Glycosylation: A new signaling paradigm for the neurovascular diseases.

A wide range of life-threatening conditions with complicated pathogenesis involves neurovascular disorders encompassing Neurovascular unit (NVU) damage. The pathophysiology of NVU is characterized by several features including tissue hypoxia, stimulation of inflammatory and angiogenic processes, and the initiation of intricate molecular interactions, collectively leading to an elevation in blood-brain barrier permeability, atherosclerosis and ultimately, neurovascular diseases. The presence of compelling data about the significant involvement of the glycosylation in the development of diseases has sparked a discussion on whether the abnormal glycosylation may serve as a causal factor for neurovascular disorders, rather than being just recruited as a secondary player in regulating the critical events during the development processes like embryo growth and angiogenesis. An essential tool for both developing new anti-ischemic therapies and understanding the processes of ischemic brain damage is undertaking pre-clinical studies of neurovascular disorders. Together with the post-translational modification of proteins, the modulation of glycosylation and its enzymes implicates itself in several abnormal activities which are known to accelerate neuronal vasculopathy. Despite the failure of the majority of glycosylation-based preclinical and clinical studies over the past years, there is a significant probability to provide neuroprotection utilizing modern and advanced approaches to target abnormal glycosylation activity at embryonic stages as well. This article focuses on a variety of experimental evidence to postulate the interconnection between glycosylation and vascular disorders along with possible treatment options.

Therapeutic insights elaborating the potential of retinoids in Alzheimer's disease.

Alzheimer's disease (AD) is perceived with various pathophysiological characteristics such oxidative stress, senile plaques, neuroinflammation, altered neurotransmission immunological changes, neurodegenerative pathways, and age-linked alterations. A great deal of studies even now are carried out for comprehensive understanding of pathological processes of AD, though many agents are in clinical trials for the treatment of AD. Retinoids and retinoic acid receptors (RARs) are pertinent to such attributes of the disease. Retinoids support the proper functioning of the immunological pathways, and are very potent immunomodulators. The nervous system relies heavily on retinoic acid signaling. The disruption of retinoid signaling relates to several pathogenic mechanisms in the normal brain. Retinoids play critical functions in the neuronal organization, differentiation, and axonal growth in the normal functioning of the brain. Disturbed retinoic acid signaling causes inflammatory responses, mitochondrial impairment, oxidative stress, and neurodegeneration, leading to Alzheimer's disease (AD) progression. Retinoids interfere with the production and release of neuroinflammatory chemokines and cytokines which are located to be activated in the pathogenesis of AD. Also, stimulating nuclear retinoid receptors reduces amyloid aggregation, lowers neurodegeneration, and thus restricts Alzheimer's disease progression in preclinical studies. We outlined the physiology of retinoids in this review, focusing on their possible neuroprotective actions, which will aid in elucidating the critical function of such receptors in AD pathogenesis.

Exploring the potential role of rab5 protein in endo-lysosomal impairment in Alzheimer's disease.

Growing evidence suggests that neuronal dysfunction in the endo-lysosomal and autophagic processes contributes to the onset and progression of neurodegenerative diseases such as Alzheimer's disease (AD). Since they are the primary cellular systems involved in the production and clearance of aggregated amyloid plaques, endo-lysosomal or autophagic equilibrium must be maintained throughout life. As a result, variations in the autophagic and endo-lysosomal torrent, as a measure of degenerative function in these sections or pathways, may have a direct impact on disease-related processes, such as Aß clearance from the brain and interneuronal deposition of Aß and tau aggregates, thus disrupting synaptic plasticity. The discovery of several chromosomal factors for Alzheimer's disease that are clinically linked to regulation of the endocytic pathway, including protein aggregation and removal, supports the theory that the endo-lysosomal/autophagic torrent is more susceptible to impairment, especially as people age, thus catalysing the onset of disease. Although the role of endo-lysosomal/autophagic dysfunction in neurodegeneration has progressed in recent years, the field remains underdeveloped. Because of its possible therapeutic implications in Alzheimer's disease, further study is needed to explain the possibilities for effective autophagy regulation.

Unravelling the potential neuroprotective facets of erythropoietin for the treatment of Alzheimer's disease.

During the last three decades, recombinant DNA technology has produced a wide range of hematopoietic and neurotrophic growth factors, including erythropoietin (EPO), which has emerged as a promising protein drug in the treatment of several diseases. Cumulative studies have recently indicated the neuroprotective role of EPO in preclinical models of acute and chronic neurodegenerative disorders, including Alzheimer's disease (AD). AD is one of the most prevalent neurodegenerative illnesses in the elderly, characterized by the accumulation of extracellular amyloid-ß (Aß) plaques and intracellular neurofibrillary tangles (NFTs), which serve as the disease's two hallmarks. Unfortunately, AD lacks a successful treatment strategy due to its multifaceted and complex pathology. Various clinical studies, both in vitro and in vivo, have been conducted to identify the various mechanisms by which erythropoietin exerts its neuroprotective effects. The results of clinical trials in patients with AD are also promising. Herein, it is summarized and reviews all such studies demonstrating erythropoietin's potential therapeutic benefits as a pleiotropic neuroprotective agent in the treatment of Alzheimer's disease.

Deciphering the focal role of endostatin in Alzheimer's disease.

Alzheimer's disease (AD) is a paramount chronic neurodegenerative condition that has been affecting elderly people since the 1900s. It causes memory loss, disorientation, and poor mental function. AD is considered to be one of the most serious problems that dementia sufferers face. Despite extensive investigation, the pathological origin of Alzheimer's disease remains a mystery. The amyloid cascade theory and the vascular hypothesis, which stresses the buildup of Aß plaques, have dominated research into dementia and aging throughout history. However, research into this task failed to yield the long-awaited therapeutic miracle lead for Alzheimer's disease. Perhaps a hypothetical fragility in the context of Alzheimer's disease was regarded as a state distinct from aging in general, as suggested by the angiogenesis hypothesis, which suggests that old age is one state associated with upregulation of angiogenic growth factors, resulting in decreased microcirculation throughout the body. There has also been evidence that by controlling or inhibiting the components involved in the sequence of events that cause angiogenesis, there is a visible progression in AD patients. In Alzheimer's disease, one such antiangiogenic drug is being used.

Multifaceted Alzheimer's Disease: Building a Roadmap for Advancement of Novel Therapies.

Alzheimer's disease (AD) is one of the most prevailing neurodegenerative disorders of elderly humans associated with cognitive damage. Biochemical, epigenetic, and pathophysiological factors all consider a critical role of extracellular amyloid-beta (Aß) plaques and intracellular neurofibrillary tangles (NFTs) as pathological hallmarks of AD. In an endeavor to describe the intricacy and multifaceted nature of AD, several hypotheses based on the roles of Aß accumulation, tau hyperphosphorylation, impaired cholinergic signaling, neuroinflammation, and autophagy during the initiation and advancement of the disease have been suggested. However, in no way do these theories have the potential of autonomously describing the pathophysiological alterations located in AD. The complex pathological nature of AD has hindered the recognition and authentication of successful biomarkers for the progression of its diagnosis and therapeutic strategies. There has been a significant research effort to design multi-target-directed ligands for the treatment of AD, an approach which is developed by the knowledge that AD is a composite and multifaceted disease linked with several separate but integrated molecular pathways.

Decrypting the potential role of α-lipoic acid in Alzheimer's disease.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases with motor disturbances, cognitive decline, and behavioral impairment. It is characterized by the extracellular aggregation of amyloid-ß plaques and the intracellular accumulation of tau protein. AD patients show a cognitive decline, which has been associated with oxidative stress, as well as mitochondrial dysfunction. Alpha-lipoic acid (α-LA), a natural antioxidant present in food and used as a dietary supplement, has been considered a promising agent for the prevention or treatment of neurodegenerative disorders. Despite multiple preclinical studies indicating beneficial effects of α-LA in memory functioning, and pointing to its neuroprotective effects, to date only a few studies have examined its effects in humans. Studies performed in animal models of memory loss associated with aging and AD have shown that α-LA improves memory in a variety of behavioral paradigms. Furthermore, molecular mechanisms underlying α-LA effects have also been investigated. Accordingly, α-LA shows antioxidant, antiapoptotic, anti-inflammatory, glioprotective, metal chelating properties in both in vivo and in vitro studies. In addition, it has been shown that α-LA reverses age-associated loss of neurotransmitters and their receptors. The review article aimed at summarizing and discussing the main studies investigating the neuroprotective effects of α-LA on cognition as well as its molecular effects, to improve the understanding of the therapeutic potential of α-LA in patients suffering from neurodegenerative disorders, supporting the development of clinical trials with α-LA.

Role of Monoamine Oxidase Activity in Alzheimer's Disease: An Insight into the Therapeutic Potential of Inhibitors.

Despite not being utilized as considerably as other antidepressants in the therapy of depression, the monoamine oxidase inhibitors (MAOIs) proceed to hold a place in neurodegeneration and to have a somewhat broad spectrum in respect of the treatment of neurological and psychiatric conditions. Preclinical and clinical studies on MAOIs have been developing in recent times, especially on account of rousing discoveries manifesting that these drugs possess neuroprotective activities. The altered brain levels of monoamine neurotransmitters due to monoamine oxidase (MAO) are directly associated with various neuropsychiatric conditions like Alzheimer's disease (AD). Activated MAO induces the amyloid-beta (Aß) deposition via abnormal cleavage of the amyloid precursor protein (APP). Additionally, activated MAO contributes to the generation of neurofibrillary tangles and cognitive impairment due to neuronal loss. No matter the attention of researchers on the participation of MAOIs in neuroprotection has been on monoamine oxidase-B (MAO-B) inhibitors, there is a developing frame of proof indicating that monoamine oxidase-A (MAO-A) inhibitors may also play a role in neuroprotection. The therapeutic potential of MAOIs alongside the complete understanding of the enzyme's physiology may lead to the future advancement of these drugs.