Multiple sclerosis treatments a review of current biomedical engineering approaches.

Multiple Sclerosis (MS) is an autoimmune condition targeting the central nervous system (CNS) characterized by focal demyelination with inflammation, causing neurodegeneration and gliosis. This is accompanied by a refractory period in relapsing MS or chronic progression in primary progressive MS. Current MS treatments target disease relapses and aim to reduce further demyelination and disability. These include the treatment of acute exacerbations through global immunomodulation upon corticosteroid administration, which are accompanied by adverse reactions. Disease modifying therapies (DMTs) which provide targeted immunosuppression of T and B cells, and sequestration of leukocytes out of CNS, have led to further improvements in demyelination prevention and disease burden reduction. Despite their efficacy, DMTs are ineffective in remyelination, pathology reversal and have minimal effects in progressive MS. The advent of modern biomedical engineering approaches in combination with a better understanding of MS pathology, has led to the development of novel, regenerative approaches to treatment. Such treatments utilize neural stem cells (NSCs) and can reduce disease relapses and reverse damage caused by the disease through localized tissue regeneration. While at initial stages, pre-clinical and clinical studies utilizing NSCs and immune modulation have shown promising outcomes in tissue regeneration, creating a potential new era in MS therapy.

Association between osteoarthritis with Parkinson's disease in the US (NHANES 2011-2020).

Objected: To evaluate the association between osteoarthritis (OA) and Parkinson's disease (PD) in adults in the United States. Methods: Using 2011-2020 NHANES data, a cross-sectional study of 11,117 adults over the age of 40 was conducted. Univariate logistic regression and multivariate logistic regression were used to analyze the relationship between arthritis and PD. In addition, stratified analysis was used to examine whether the relationship between arthritis and PD was interactive with age, gender, race, education, BMI. Results: In this study, a total of 11,117 participants were included, and we found that osteoarthritis was positively correlated with the development of PD compared with non-arthritis patients [1.95 (1.44 ~ 2.62)] (p < 0.001). After adjusting the covariates, the results are still stable. Conclusion: PD patients were positively correlated with OA. Among people with OA, there was a 95% increased risk of PD compared to people without arthritis. Therefore, when treating OA, attention should be paid to the increased risk of PD. In the meantime, further studies are needed to explore the link between OA and PD patients.

Intercellular Highways in Transport Processes.

Communication among cells is vital in multicellular organisms. Various structures and mechanisms have evolved over time to achieve the intricate flow of material and information during this process. One such way of communication is through tunnelling membrane nanotubes (TNTs), which were initially described in 2004. These TNTs are membrane-bounded actin-rich cellular extensions, facilitating direct communication between distant cells. They exhibit remarkable diversity in terms of structure, morphology, and function, in which cytoskeletal proteins play an essential role. Biologically, TNTs play a crucial role in transporting membrane components, cell organelles, and nucleic acids, and they also present opportunities for the efficient transmission of bacteria and viruses, furthermore, may contribute to the dissemination of misfolded proteins in certain neurodegenerative diseases. Convincing results of studies conducted both in vitro and in vivo indicate that TNTs play roles in various biomedical processes, including cell differentiation, tissue regeneration, neurodegenerative diseases, immune response and function, as well as tumorigenesis.

The Relationship among SARS-CoV-2, Vaccine Spike Protein, Renin- Angiotensin System, and Epilepsy.

Several comorbidities and illnesses have emerged after the COVID-19 pandemic and the introduction of vaccination based on a slightly modified SARS-CoV-2 spike protein. One of these diseases is epilepsy, where the dysfunctional RAS plays a crucial role in the propagation of the disorder. SARS-CoV-2 infects host cells by utilizing the angiotensin-converting enzyme Type 2 (ACE2) receptor, which allows the virus to infect various cell types, including those in the lungs, nasopharynx, kidneys, lymph nodes, small intestine, stomach, spleen, and brain, leading to widespread organ damage. Once SARS-CoV-2 binds to the ACE2 receptor, it can lead to the overactivation of the ACE/Ang II/AT1R axis. Consequently, higher levels of Ang II activate several deleterious pathways that promote inflammation, contributing to inflammatory responses in the body and exacerbating conditions such as seizures. Additionally, the excitatory effect of AT1R by Ang II excess due to ACE2 inhibition by SARS-CoV-2 or by the vaccine Spike protein may play a further role in the mechanism contributing to epilepsy.

Bifunctional Inhibitor Lentinan Inhibits Fibrillogenesis of Amyloid-ß Protein and α-Synuclein and Alleviates Their Cytotoxicity: In Vitro and In Vivo Studies.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative diseases in the world. Misfolding of ß-amyloid (Aß) and α-synuclein (α-syn) and subsequent fibril formation are closely associated with the pathogenesis of AD and PD, respectively. Lentinan is a natural product commonly used in medicine and dietary supplements. It has potential antitumor, anti-inflammatory, and antiviral effects, but the underlying mechanism of its action on AD and PD remains unclear. In this study, lentinan inhibited the formation of Aß and α-syn fibers in a dose-dependent manner and disrupted their mature fibers. Lentinan inhibited the conversion of Aß and α-syn conformations to ß-sheet-rich conformations. Additionally, lentinan protected Caenorhabditis elegans against damage caused by the accumulation of Aß and α-syn aggregation and prolonged their lifespan. Notably, the beneficial effects of lentinan in AD and PD mice were also demonstrated, including ameliorating the cognitive and memory impairments in AD mice and behavioral deficits in PD mice. Finally, molecular interactions between lentinan and Aß/α-syn pentamers were also explored using molecular docking.

Evaluating the safety and efficiency of nanomaterials: A focus on mitochondrial health.

Nanomaterials (NMs) have extensive application potential in drug delivery, tissue engineering, and various other domains, attributable to their exceptional physical and chemical properties. Nevertheless, an increasing body of literature underscores the diverse safety risks are associated with NMs upon interaction with the human body, including oxidative stress and programmed cell death. Mitochondria, serving as cellular energy factories, play a pivotal role in energy metabolism and the regulation of cell fate. Organs with substantial energy demands, including the heart and brain, are highly sensitive to mitochondrial integrity, with mitochondrial impairment potentially resulting in significant dysfunction and pathologies such as as heart failure and neurodegenerative disease. This review elucidates the pathways by which NMs translocate into mitochondria, their intracellular dynamics, and their impact on mitochondrial morphology, respiratory chain activity, and metabolic processes. We further investigate associated molecular mechanisms, including mitochondrial dynamic imbalance, calcium overload, and oxidative stress, and elucidate the pivotal roles of mitochondria in different forms of programmed cell death such as apoptosis and autophagy. Finally, we offer recommendations regarding the safety and efficacy of NMs for medical applications. By systematically analyzing the interactions and molecular mechanisms between NMs and mitochondria, this paper aims to enhance the toxicological evaluation framework of NMs and provide a foundational reference and theoretical basis for their clinical utilization.

Neuroenergetic alterations in neurodegenerative diseases: A systematic review and meta-analysis of in vivo31P-MRS studies.

Phosphorus magnetic resonance spectroscopy (31P-MRS) is applied for non-invasive studies of neuroenergetic metabolism in neurodegenerative diseases. However, the findings are inconsistent and have not yet been tested in meta-analyses. To address this gap, we performed a systematic review of 29 studies and conducted meta-analyses for 9 studies on Alzheimer's disease (AD, n = 140 patients), 9 studies on Parkinson's disease (PD, n = 183 patients), 3 studies on Progressive Supranuclear Palsy (PSP, n = 42 patients), and 2 studies on Multiple System Atrophy (MSA, n = 24 patients). Compared to controls, AD patients had a higher ratio of phosphomonoesters/phosphodiesters (PME/PDE) in the frontal lobe (MD = 0.049, p = 0.0003); PD patients showed decreases in PME/PDE in the putamen (MD = -0.050, p = 0.023) and adenosine triphosphate/inorganic phosphate (ATP/Pi) in the midbrain (MD = -0.274, p = 0.002); PSP patients presented increased phosphocreatine (PCr)/Pi in the basal ganglia (MD = 0.556, p = 0.030) and adenosine diphosphate (ADP)/Pi in the occipital lobe (MD = 0.005, p = 0.009); no significant effects were observed in MSA. Here, our review underlines the importance of 31P-MRS in the characterization of distinct neuroenergetic changes and its potential to improve the diagnosis and follow-up of neurodegenerative diseases.

Ageing, proteostasis, and the gut: Insights into neurological health and disease.

Recent research has illuminated the profound bidirectional communication between the gastrointestinal tract and the brain, furthering our understanding of neurological ailments facilitating possible therapeutic strategies. Technological advancements in high-throughput sequencing and multi-omics have unveiled significant alterations in gut microbiota and their metabolites in various neurological disorders. This review provides a thorough analysis of the role of microbiome-gut-brain axis in neurodegenerative disease pathology, linking it to reduced age-associated proteostasis. We discuss evidences that substantiate the existence of a gut-brain cross talk ranging from early clinical accounts of James Parkinson to Braak's hypothesis. In addition to understanding of microbes, the review particularly entails specific metabolites which are altered in neurodegenerative diseases. The regulatory effects of microbial metabolites on protein clearance mechanisms, proposing their potential therapeutic implications, are also discussed. By integrating this information, we advocate for a combinatory therapeutic strategy that targets early intervention, aiming to restore proteostasis and ameliorate disease progression. This approach not only provides a new perspective on the pathogenesis of neurodegenerative diseases but also highlights innovative strategies to combat the increasing burden of these age-related disorders.

Recent advances in two-dimensional materials for the diagnosis and treatment of neurodegenerative diseases.

With the size of the aging population increasing worldwide, the effective diagnosis and treatment of neurodegenerative diseases (NDDs) has become more important. Two-dimensional (2D) materials offer specific advantages for the diagnosis and treatment of NDDs due to their high sensitivity, selectivity, stability, and biocompatibility, as well as their excellent physical and chemical characteristics. As such, 2D materials offer a promising avenue for the development of highly sensitive, selective, and biocompatible theragnostics. This review provides an interdisciplinary overview of advanced 2D materials and their use in biosensors, drug delivery, and tissue engineering/regenerative medicine for the diagnosis and/or treatment of NDDs. The development of 2D material-based biosensors has enabled the early detection and monitoring of NDDs via the precise detection of biomarkers or biological changes, while 2D material-based drug delivery systems offer the targeted and controlled release of therapeutics to the brain, crossing the blood-brain barrier and enhancing treatment effectiveness. In addition, when used in tissue engineering and regenerative medicine, 2D materials facilitate cell growth, differentiation, and tissue regeneration to restore neuronal functions and repair damaged neural networks. Overall, 2D materials show great promise for use in the advanced treatment of NDDs, thus improving the quality of life for patients in an aging population.

The Role of Glucagon-Like Peptide-1 Agonists in the Treatment of Multiple Sclerosis: A Narrative Review.

Multiple sclerosis (MS) is a chronic, progressive autoimmune disease modulated by autoantibodies that inflame and destroy the myelin sheath encasing neuronal axons, impairing proper axonal conduction and function. Glucagon-like peptide-1 (GLP-1) receptor agonists have been demonstrated to exert anti-inflammatory and neuroprotective effects, making these drugs particularly exciting prospects in the treatment of MS. While the exact mechanism remains unclear, GLP-1 receptor agonists may modulate inflammatory responses by targeting GLP-1 receptors present on immune cells such as macrophages, monocytes, and lymphocytes. In animal models, GLP-1 agonists have been shown to significantly delay the onset and severity of experimental autoimmune encephalopathy symptoms, as well as to increase nerve myelination and brain weight. In further experiments using animal models of nerve crush injury, specimens given GLP-1 agonists reported a significant increase in the rate and density of nerve regeneration compared to controls. Thus, GLP-1 agonists show promise as both prophylactic and symptomatic treatment for MS and may provide further utility in the treatment of other autoimmune, inflammatory, and neurodegenerative conditions.

Autophagy-lysosomal-associated neuronal death in neurodegenerative disease.

Autophagy, the major lysosomal pathway for degrading damaged or obsolete constituents, protects neurons by eliminating toxic organelles and peptides, restoring nutrient and energy homeostasis, and inhibiting apoptosis. These functions are especially vital in neurons, which are postmitotic and must survive for many decades while confronting mounting challenges of cell aging. Autophagy failure, especially related to the declining lysosomal ("phagy") functions, heightens the neuron's vulnerability to genetic and environmental factors underlying Alzheimer's disease (AD) and other late-age onset neurodegenerative diseases. Components of the global autophagy-lysosomal pathway and the closely integrated endolysosomal system are increasingly implicated as primary targets of these disorders. In AD, an imbalance between heightened autophagy induction and diminished lysosomal function in highly vulnerable pyramidal neuron populations yields an intracellular lysosomal build-up of undegraded substrates, including APP-ßCTF, an inhibitor of lysosomal acidification, and membrane-damaging Aß peptide. In the most compromised of these neurons, ß-amyloid accumulates intraneuronally in plaque-like aggregates that become extracellular senile plaques when these neurons die, reflecting an "inside-out" origin of amyloid plaques seen in human AD brain and in mouse models of AD pathology. In this review, the author describes the importance of lysosomal-dependent neuronal cell death in AD associated with uniquely extreme autophagy pathology (PANTHOS) which is described as triggered by lysosomal membrane permeability during the earliest "intraneuronal" stage of AD. Effectors of other cell death cascades, notably calcium-activated calpains and protein kinases, contribute to lysosomal injury that induces leakage of cathepsins and activation of additional death cascades. Subsequent events in AD, such as microglial invasion and neuroinflammation, induce further cytotoxicity. In major neurodegenerative disease models, neuronal death and ensuing neuropathologies are substantially remediable by reversing underlying primary lysosomal deficits, thus implicating lysosomal failure and autophagy dysfunction as primary triggers of lysosomal-dependent cell death and AD pathogenesis and as promising therapeutic targets.

The Impact of Aging on HIV-1-related Neurocognitive Impairment.

Depending on the population studied, HIV-1-related neurocognitive impairment is estimated to impact up to half the population of people living with HIV (PLWH) despite the availability of combination antiretroviral therapy (cART). Various factors contribute to this neurocognitive impairment, which complicates our understanding of the molecular mechanisms involved. Biological aging has been implicated as one factor possibly impacting the development and progression of HIV-1-related neurocognitive impairment. This is increasingly important as the life expectancy of PLWH with virologic suppression on cART is currently projected to be similar to that of individuals not living with HIV. Based on our increasing understanding of the biological aging process on a cellular level, we aim to dissect possible interactions of aging- and HIV-1 infection-induced effects and their role in neurocognitive decline. Thus, we begin by providing a brief overview of the clinical aspects of HIV-1-related neurocognitive impairment and review the accumulating evidence implicating aging in its development (Part I). We then discuss potential interactions between aging-associated pathways and HIV-1-induced effects at the molecular level (Part II).

Reimagining Day Rehabilitation For Frailty and Neurodegenerative Conditions through the integrated Rehabilitation and EnAblement Program (iREAP).

Background: integrated Rehabilitation and EnAblement Program (iREAP) is an innovative redesign of the traditional day rehabilitation model, providing an anticipatory, early assessment and intervention program that manages care of community-dwelling older people with complex needs. It coordinates access to disciplines across medical, allied health and nursing, with a self-management focus, partnering with primary health in an integrated approach. Objective: This observational study reviews the effectiveness of iREAP on frailty, patient activation, quality of life and physical outcome measures on older people at risk of, or experiencing falls and frailty, or with neurodegenerative conditions, including Parkinson's Disease. Methods: 99 participants completed the eight-week multidisciplinary program. Patient outcome measures included Rockwood Clinical Frailty Scale, quality of life measures, Patient Activation Measure, Timed Up and Go, 6 Minute Walk Test and Berg Balance Scale. Results: On completion of iREAP, participants displayed improvements in their Rockwood Clinical Frailty Scores (mildly frail to vulnerable), 'patient activation' (55.08 to 60.61), quality of life (Parkinson's Disease Questionnaire-39, 49.93 to 47.16; WHO Quality of Life - Bref physical domain, 21 to 22.7) and physical measures including balance (44 to 49/56 Berg Balance scale) and mobility (294 m to 336 m, 6-minute walk test). Falls were not reduced at twelve months post-program (3.40 to 2.01). Conclusion: iREAP is an interdisciplinary, early assessment and intervention program with the potential to reverse frailty and improve quality of life for complex older patients. This paper offers a platform for future research, given the paucity of evidence reviewing the efficacy of integrated anticipatory models of care in older adults with complex needs.

Development of a General Composite Scale (GENCOMS) for Progressive Neurodegenerative Diseases and Implications for the Assessment of Disease-Modifying Therapies.

INTRODUCTION: The reliable assessment of treatment outcomes for disease-modifying therapies (DMT) in neurodegenerative disease is challenging. The objective of this paper is to describe a generalized framework for developing composite scales that can be applied in diverse, degenerative conditions, termed "GENCOMS." Composite scales optimize the sensitivity for detecting clinically meaningful effects that slow disease progression. METHODS: The GENCOMS method relies on robust natural history data and/or placebo arm data from DMT trials. Validated scales that are core to the disease process have been identified, and item level data obtained to standardize the response outcomes from 0 (best possible score) to 1 (worst possible score). A partial least squares regression analysis was conducted with temporal change as the dependent variable and change scores in standardized items as the explanatory variables. The derived model coefficients constitute a weighted sum of items that most effectively measure disease progression. RESULTS: The resultant composite scale was optimized to detect disease progression and can be examined in a range of slow or fast progressing populations. The scale can be used in studies with comparable patient populations as an endpoint optimized to measure disease progression and therefore ideally suited to assess treatment effects in DMTs. CONCLUSION: The methodology presented here provides a generalizable framework for developing composite scales in the assessment of neurodegenerative disease progression and evaluation of DMT effects. By objectively selecting and weighting items from previously validated measures based solely on their sensitivity to disease progression, this methodology allows for the creation of a more responsive measurement of clinical decline. This heightened sensitivity to clinical decline can be utilized to detect modest yet meaningful treatment effects in the early stages of neurogenerative diseases, when it is optimal to begin a DMT.

Copper homeostasis and cuproptosis in health and disease.

Copper is a vital trace element in human physiology, essential for the synthesis of numerous crucial metabolic enzymes and facilitation of various biological processes. Regulation of copper levels within a narrow range is imperative for maintaining metabolic homeostasis. Numerous studies have demonstrated the significant roles of copper homeostasis and cuproptosis in health and disease pathogenesis. However, a comprehensive and up-to-date systematic review in this domain remains absent. This review aims to consolidate recent advancements in understanding the roles of cuproptosis and copper homeostasis in health and disease, focusing on the underlying mechanisms and potential therapeutic interventions. Dysregulation of copper homeostasis, manifesting as either copper excess or deficiency, is implicated in the etiology of various diseases. Cuproptosis, a recently identified form of cell death, is characterized by intracellular copper overload. This phenomenon mediates a diverse array of evolutionary processes in organisms, spanning from health to disease, and is implicated in genetic disorders, liver diseases, neurodegenerative disorders, and various cancers. This review provides a comprehensive summary of the pathogenic mechanisms underlying cuproptosis and copper homeostasis, along with associated targeted therapeutic agents. Furthermore, it explores future research directions with the potential to yield significant advancements in disease treatment, health management, and disease prevention.

Body Composition, Vascular Health, Cardiorespiratory Fitness, Lung Function, Muscle Architecture, and Physical Activity in People with Young Onset Dementia: A Case-Control Study.

BACKGROUND: Body composition, blood pressure, estimated maximal oxygen uptake (VO2max), lung function, physical activity, muscle architecture, and endothelial function had not previously been examined in people with young onset dementia. Therefore, the study measured these variables in a young onset dementia group, compared them to age-matched controls. METHODS: Estimated VO2max (via the Astrand-Rhyming test), body composition, blood pressure, lung function (via spirometry), muscle architecture (via ultrasonography) and endothelial function (via flow mediated dilation) were assessed. Physical activity was measured using ActiGraph accelerometers for 7 days. RESULTS: We recruited 33 participants (16 young onset dementia, 17 controls). The young onset dementia group had shorter fascicle lengths of the vastus lateralis, were sedentary for longer over a seven-day period, and completed less moderate-vigorous physical activity than controls (p=0.028, d=0.81; large effect, p=0.029, d=0.54; moderate effect, and p=0.014, d=0.97; large effect, respectively for pairwise comparisons). Pairwise comparisons suggest no differences at the p<0.05 level between young onset dementia and controls for estimated VO2max (despite a moderate effect size [d=0.66]), height, body mass, BMI, blood pressure, light physical activity, lung function, muscle thickness, pennation angle, or endothelial function. CONCLUSION: This study highlights differences between people with young onset dementia and controls, underscoring the need for multicomponent exercise interventions. Future interventions should target muscle architecture, increase moderate-vigorous physical activity, and reduce sedentariness, with the goal of improving quality of life and promoting functional independence.

Emerging insights into traditional Chinese medicine associated with neurodegenerative diseases: A bibliometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Research suggests that traditional Chinese medicine (TCM) holds promise in offering innovative approaches to tackle neurodegenerative disorders. In our endeavor, we conducted a comprehensive bibliometric analysis to delve into the landscape of TCM research within the realm of neurodegenerative diseases, aiming to uncover the present scenario, breadth, and trends in this field. This analysis presents potentially valuable insights for the clinical application of traditional Chinese medicine and provides compelling evidence supporting its efficacy in the treatment of neurodegenerative conditions. AIM OF THE STUDY: The incidence of neurodegenerative diseases is on the rise, yet effective treatments are still lacking. Research indicates that TCM could offer novel perspectives for addressing neurodegenerative conditions. Nonetheless, the literature on this topic is intricate and multifaceted, with existing reviews offering only limited coverage. To gain a thorough understanding of TCM research in neurodegenerative diseases, we undertook a bibliometric analysis to explore the current status, scope, and trends in this area. MATERIALS AND METHODS: A literature search was carried out on April 1, 2024, utilizing the Web of Science Core Collection (WoSCC). Visualization and quantitative analyses were then performed with the assistance of CiteSpace, VOSviewer, and R software. RESULTS: A total of 6856 articles were retrieved in the search. Research on TCM for neurodegenerative diseases commenced in 1989 and has exhibited a notable overall growth since then. Main research contributors include East Asian countries like China, as well as the United States. Through our analysis, we identified 15 highly productive authors, 10 top-tier journals, 13 citation clusters, 11 influential articles, and observed a progression in keyword evolution across 4 distinct categories. In 2020, there was a significant upsurge in the knowledge base, collaboration efforts, and publication output within the field. This field is interdisciplinary: network pharmacology emerges as the cutting-edge paradigm in TCM research, while Alzheimer's disease remains a prominent focus among neurodegenerative conditions due to its evolving etiology. A burst detection analysis unveils that in 2024, the focal points of research convergence between TCM and neurodegenerative diseases lie in two key biological processes or mechanisms: autophagy and microbiota. CONCLUSIONS: For the first time, this study quantitatively and visually captures the evolution of TCM in addressing neurodegenerative diseases, showcasing a notable acceleration in recent years. Our findings underscore the pivotal role of interdisciplinary collaboration and the necessity for increased global partnerships. Network pharmacology, leveraging the advancements of the big data era, embraces a holistic and systematic approach as a novel paradigm in exploring traditional Chinese medicine and unraveling their fundamental mechanisms. Three ethnomedical plants-Tianma, Renshen, and Wuweizi-demonstrate the promise of their bioactive compounds in treating neurodegenerative disorders, bolstered by their extensive historical usage for such ailments. Moreover, our intricate analysis of the evolutionary trajectories of key themes such as targets and biomarkers substantially enriches our comprehension of the underlying mechanisms involved.

Sleep fragmentation despite intact rest-activity patterns in premanifest Huntington's disease: An actigraphy study.

OBJECTIVE: Sleep research in Huntington's disease (HD) has primarily focused on manifest HD, with significantly less attention given to premanifest HD (Pre-HD). Therefore, we investigated sleep and rest-activity patterns in people with Pre-HD versus healthy controls (HC). METHODS: We conducted a cross-sectional study including 36 Pre-HD and 48 HC participants. Pre-HD participants were stratified into three groups according to their proximity to estimated diagnosis, using a cytosine-adenine-guanine (CAG) and current age-based predictive model: NEAR (<9 years to diagnosis), MID (9-15 years to diagnosis) and FAR (>15 years to diagnosis). Sleep and rest-activity patterns were assessed using wrist-worn actigraphy, a sleep diary, and sleep questionnaires. RESULTS: NEAR and MID groups experienced higher fragmentation index than HC and FAR groups. NEAR and MID groups also exhibited greater WASO than the FAR group. NEAR and MID groups showed lower intra-daily variability (IV) than HC and FAR groups, with the NEAR group also being more active in the most active 10 h (M10). Groups did not differ on subjective sleep measures, inter-daily stability (IS), sleep regularity index, relative amplitude, or amount of activity in the least active 5 h (L5). Considering all Pre-HD participants, fewer years to diagnosis, higher CAG-age-product (CAP) scores (a measure of cumulative exposure to the HD-causing gene mutation) and larger CAG repeat lengths correlated with higher WASO, fragmentation index, L5, IS, and lower sleep efficiency and IV. Higher CAP score correlated with higher M10. CONCLUSIONS: Despite intact rest-activity patterns and similar subjective sleep quality to HC, greater sleep fragmentation is a prominent and early feature in Pre-HD. Therefore, reducing sleep fragmentation may be a potential target for sleep intervention in HD. Longitudinal studies using larger samples are needed to assess sleep across the disease spectrum and its impact on clinical outcomes, like cognition.

From mitochondrial dysfunction to neuroinflammation in Parkinson's disease: Pathogenesis and mitochondrial therapeutic approaches.

Parkinson's disease (PD) is a prevalent and intricate neurological condition resulting from a combination of several factors, such as genetics, environment, and the natural process of aging. Degeneration of neurons in the substantia nigra pars compacta (SN) can cause motor and non-motor impairments in patients with PD. In PD's etiology, inflammation and mitochondrial dysfunction play significant roles in the disease's development. Studies of individuals with PD have revealed increased inflammation in various brain areas. Furthermore, mitochondrial dysfunction is an essential part of PD pathophysiology. Defects in the components of the mitochondrial nucleus, its membrane or internal signaling pathways, mitochondrial homeostasis, and morphological alterations in peripheral cells have been extensively documented in PD patients. According to these studies, neuroinflammation and mitochondrial dysfunction are closely connected as pathogenic conditions in neurodegenerative diseases like PD. Given the mitochondria's role in cellular homeostasis maintenance in response to membrane structural flaws or mutations in mitochondrial DNA, their dynamic nature may present therapeutic prospects in this area. Recent research investigates mitochondrial transplantation as a potential treatment for Parkinson's disease in damaged neurons. This review delves into the impact of inflammation and mitochondrial dysfunction on PD occurrence, treatment approaches, and the latest developments in mitochondrial transplantation, highlighting the potential consequences of these discoveries.

Two novel DnaJ chaperone proteins CG5001 and P58IPK regulate the pathogenicity of Huntington's disease related aggregates.

Huntington's disease (HD) is a rare neurodegenerative disease caused due to aggregation of Huntingtin (HTT) protein. This study involves the cloning of 40 DnaJ chaperones from Drosophila, and overexpressing them in yeasts and fly models of HD. Accordingly, DnaJ chaperones were catalogued as enhancers or suppressors based on their growth phenotypes and aggregation properties. 2 of the chaperones that came up as targets were CG5001 and P58IPK. Protein aggregation and slow growth phenotype was rescued in yeasts, S2 cells, and Drosophila transgenic lines of HTT103Q with these overexpressed chaperones. Since DnaJ chaperones have protein sequence similarity across species, they can be used as possible tools to combat the effects of neurodegenerative diseases.