Inflammasome Molecular Insights in Autoimmune Diseases.

Autoimmune diseases (AIDs) emerge due to an irregular immune response towards self- and non-self-antigens. Inflammation commonly accompanies these conditions, with inflammatory factors and inflammasomes playing pivotal roles in their progression. Key concepts in molecular biology, inflammation, and molecular mimicry are crucial to understanding AID development. Exposure to foreign antigens can cause inflammation, potentially leading to AIDs through molecular mimicry triggered by cross-reactive epitopes. Molecular mimicry emerges as a key mechanism by which infectious or chemical agents trigger autoimmunity. In certain susceptible individuals, autoreactive T or B cells may be activated by a foreign antigen due to resemblances between foreign and self-peptides. Chronic inflammation, typically driven by abnormal immune responses, is strongly associated with AID pathogenesis. Inflammasomes, which are vital cytosolic multiprotein complexes assembled in response to infections and stress, are crucial to activating inflammatory processes in macrophages. Chronic inflammation, characterized by prolonged tissue injury and repair cycles, can significantly damage tissues, thereby increasing the risk of AIDs. Inhibiting inflammasomes, particularly in autoinflammatory disorders, has garnered significant interest, with pharmaceutical advancements targeting cytokines and inflammasomes showing promise in AID management.

Relevance of Surface Neuronal Protein Autoantibodies as Biomarkers in Seizure-Associated Disorders.

The detection of neuronal surface protein autoantibody-related disorders has contributed to several changes in our understanding of central nervous system autoimmunity. The clinical presentation of these disorders may be associated (or not) with tumors, and often patients develop an inexplicable onset of epilepsy, catatonic or autistic features, or memory and cognitive dysfunctions. The autoantigens in such cases have critical roles in synaptic transmission and plasticity, memory function, and process learning. For months, patients with such antibodies may be comatose or encephalopathic and yet completely recover with palliative care and immunotherapies. This paper reviews several targets of neuronal antibodies as biomarkers in seizure disorders, focusing mainly on autoantibodies, which target the extracellular domains of membrane proteins, namely leucine-rich glioma-inactivated-1 (LGI1), contactin-associated protein-like 2 (CASPR2), the N-methyl-D-aspartate receptor (NMDAR), γ-aminobutyric acid receptor-B (GABABR), the glycine receptor (GlyR), and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). In order to restore health status, limit hospitalization, and optimize results, testing these antibodies should be done locally, using internationally certified procedures for a precise and rapid diagnosis, with the possibility of initiating therapy as soon as possible.

Validity and reliability of the Romanian version of the Hill-Bone compliance to high blood pressure therapy scale.

Romania is considered a country with high cardiovascular risk, arterial hypertension and its complications accounting for about 60% of total deaths. The management of high blood pressure often involves a combination of both therapeutic regimens as well as lifestyle changes, to which patients have to be adherent. In order to assess patients adherence to professionals' recommendations, validated tools are needed. The aim of our study was to translate, culturally adapt and validate the Hill-Bone Compliance to High Blood Pressure Therapy Scale into Romanian. The study included 215 participants from Iasi, North-Eastern Romania. The internal consistency of the instrument was measured with Cronbach's alpha coefficient, while the construct validity was determined using exploratory factor analysis and principal component extraction with promax rotation. Sampling adequacy and appropriateness of data for factor analysis was measured using Kaiser-Meyer-Olkin (KMO) statistics and Bartlett's test of sphericity. Our statistical analysis revealed a Cronbach's alpha coefficient of 0.733 (73.3%) and a Kaiser-Meyer-Olkin (KMO) Measure of Sampling Adequacy of 0.697. The chi square test demonstrated that the overall perfect adherence was not significantly associated with the number of medications taken per day variable (p = 0.721). The Romanian version of the Hill-Bone Compliance to High Blood Pressure Therapy Scale demonstrated suitability for its use in evaluating adherence in the intended population.

Physical Exercise Prevents the Cognitive Decline among Older Adults in Romania.

Cognitive decline is one of the most important challenges related to the aging process, due to its important impact on individuals. Several studies have reported that physical exercise with a specific intensity and frequency is beneficial for maintaining cognitive health in the ageing population. The present study investigated the impact of general physical exercise on cognitive health in the older population in Romania. The study involved 60 individuals (60% male, 40% female), with a mean age of 60.78 years (SD = 2.97). The Health Interview Survey and The Minnesota Heart Survey assessed exercise frequency and intensity, while the Montreal Cognitive Assessment (MoCA) determined mild cognitive impairment (MCI) levels. The results of the statistical analysis showed that high-intensity physical exercise at a frequency of three to four times a week at the age of 40-50 years is recommended in order to significantly reduce cognitive decline. In addition, for the age of 60 years old, the results established that engaging in physical activities of a moderate intensity with a frequency of 2-3 times per month is sufficient to maintain healthy cognition. The findings suggest that exercise can serve as a behavioral intervention to mitigate cognitive dysfunction and complement past research on its cognitive health advantages.

JWH-182: a safe and effective synthetic cannabinoid for chemotherapy-induced neuropathic pain in preclinical models.

Chemotherapy-induced neuropathic pain (CINP), a condition with unmet treatment needs, affects over half of cancer patients treated with chemotherapeutics. Researchers have recently focused on the endocannabinoid system because of its critical role in regulating our bodies' most important functions, including pain. We used in vitro and in vivo methods to determine the toxicity profile of a synthetic cannabinoid, JWH-182, and whether it could be potentially effective for CINP alleviation. In vitro, we evaluated JWH-182 general toxicity, measuring fibroblast viability treated with various concentrations of compound, and its neuroprotection on dorsal root ganglion neurons treated with paclitaxel. In vivo, we performed an evaluation of acute and 28-day repeated dose toxicity in mice, with monitoring of health status and a complete histopathological examination. Finally, we evaluated the efficacy of JWH-182 on a CINP model in mice using specific pain assessment tests. JWH-182 has an acceptable toxicity profile, in both, in vitro and in vivo studies and it was able to significantly reduce pain perception in a CINP model in mice. However, the translation of these results to the clinic needs further investigation.

Therapeutic Implications of Renin-Angiotensin System Modulators in Alzheimer's Dementia.

The Renin-Angiotensin System (RAS) has attracted considerable interest beyond its traditional cardiovascular role due to emerging data indicating its potential involvement in neurodegenerative diseases, including Alzheimer's dementia (AD). This review investigates the therapeutic implications of RAS modulators, specifically focusing on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and renin inhibitors in AD. ACEIs, commonly used for hypertension, show promise in AD by reducing angiotensin (Ang) II levels. This reduction is significant as Ang II contributes to neuroinflammation, oxidative stress, and ß-amyloid (Aß) accumulation, all implicated in AD pathogenesis. ARBs, known for vasodilation, exhibit neuroprotection by blocking Ang II receptors, improving cerebral blood flow and cognitive decline in AD models. Renin inhibitors offer a novel approach by targeting the initial RAS step, displaying anti-inflammatory and antioxidant effects that mitigate AD degeneration. Preclinical studies demonstrate RAS regulation's favorable impact on neuroinflammation, neuronal damage, cognitive function, and Aß metabolism. Clinical trials on RAS modulators in AD are limited, but with promising results, ARBs being more effective that ACEIs in reducing cognitive decline. The varied roles of ACEIs, ARBs, and renin inhibitors in RAS modulation present a promising avenue for AD therapeutic intervention, requiring further research to potentially transform AD treatment strategies.

First Comparative Evaluation of Short-Chain Fatty Acids and Vitamin-K-Dependent Proteins Levels in Mother-Newborn Pairs at Birth.

BACKGROUND: The interplay between vitamin K (vitK) (as carboxylation cofactor, partially produced by the gut microbiota) and short-chain fatty acids (SCFAs), the end-product of fiber fermentation in the gut, has never been assessed in mother-newborn pairs, although newborns are considered vitK deficient and with sterile gut. METHODS: We collected venous blood from 45 healthy mothers with uncomplicated term pregnancies and umbilical cord blood from their newborns at birth. The concentrations of total SCFAs and hepatic/extra-hepatic vitK-dependent proteins (VKDPs), as proxies of vitK status were assayed: undercarboxylated and total matrix Gla protein (ucMGP and tMGP), undercarboxylated osteocalcin (ucOC), undercarboxylated Gla-rich protein (ucGRP), and protein induced by vitK absence II (PIVKA-II). RESULTS: We found significantly higher ucOC (18.6-fold), ucMGP (9.2-fold), and PIVKA-II (5.6-fold) levels in newborns, while tMGP (5.1-fold) and SCFAs (2.4-fold) were higher in mothers, and ucGRP was insignificantly modified. In mother-newborn pairs, only ucGRP (r = 0.746, p < 0.01) and SCFAs (r = 0.428, p = 0.01) levels were correlated. Conclusions: We report for the first time the presence of SCFAs in humans at birth, probably transferred through the placenta to the fetus. The increased circulating undercarboxylated VKDPSs in newborns revealed a higher vitamin K deficiency at the extrahepatic level compared to liver VKDPs.

Exploring the Therapeutic Potential of Cannabinoid Receptor Antagonists in Inflammation, Diabetes Mellitus, and Obesity.

Recently, research has greatly expanded the knowledge of the endocannabinoid system (ECS) and its involvement in several therapeutic applications. Cannabinoid receptors (CBRs) are present in nearly every mammalian tissue, performing a vital role in different physiological processes (neuronal development, immune modulation, energy homeostasis). The ECS has an essential role in metabolic control and lipid signaling, making it a potential target for managing conditions such as obesity and diabetes. Its malfunction is closely linked to these pathological conditions. Additionally, the immunomodulatory function of the ECS presents a promising avenue for developing new treatments for various types of acute and chronic inflammatory conditions. Preclinical investigations using peripherally restricted CBR antagonists that do not cross the BBB have shown promise for the treatment of obesity and metabolic diseases, highlighting the importance of continuing efforts to discover novel molecules with superior safety profiles. The purpose of this review is to examine the roles of CB1R and CB2Rs, as well as their antagonists, in relation to the above-mentioned disorders.

The Impact of Some Modulators of the Renin-Angiotensin System on the Scopolamine-Induced Memory Loss Mice Model.

As some of the renin-angiotensin-aldosterone system (RAAS)-dependent mechanisms underlying the cognitive performance modulation could include oxidative balance alterations, in this study we aimed to describe some of the potential interactions between RAAS modulators (Losartan and Ramipril) and oxidative stress in a typical model of memory impairment. In this study, 48 white male Swiss mice were divided into six groups and received RAAS modulators (oral administration Ramipril 4 mg/kg, Losartan 20 mg/kg) and a muscarinic receptors inhibitor (intraperitoneal injection scopolamine, 0.5 mg/kg) for 8 consecutive days. Then, 24 h after the last administration, the animals were euthanized and whole blood and brain tissues were collected. Biological samples were then processed, and biochemical analysis was carried out to assess superoxide dismutase and glutathione activities and malondialdehyde concentrations. In the present experimental conditions, we showed that RAAS modulation via the angiotensin-converting enzyme inhibition (Ramipril) and via the angiotensin II receptor blockage (Losartan) chronic treatments could lead to oxidative stress modulation in a non-selective muscarinic receptors blocker (scopolamine) animal model. Our results showed that Losartan could exhibit a significant systemic antioxidant potential partly preventing the negative oxidative effects of scopolamine and a brain antioxidant potential, mainly by inhibiting the oxidative-stress-mediated cellular damage and apoptosis. Ramipril could also minimize the oxidative-mediated damage to the lipid components of brain tissue resulting from scopolamine administration. Both blood serum and brain changes in oxidative stress status were observed following 8-day treatments with Ramipril, Losartan, scopolamine, and combinations. While the serum oxidative stress modulation observed in this study could suggest the potential effect of RAAS modulation and scopolamine administration on the circulatory system, blood vessels endothelia, and arterial tension modulation, the observed brain tissues oxidative stress modulation could lead to important information on the complex interaction between renin-angiotensin and cholinergic systems.

Exploring the Involvement of the Amyloid Precursor Protein A673T Mutation against Amyloid Pathology and Alzheimer's Disease in Relation to Therapeutic Editing Tools.

Alzheimer's disease (AD) is biologically defined as a complex neurodegenerative condition with a multilayered nature that leads to a progressive decline in cognitive function and irreversible neuronal loss. It is one of the primary diseases among elderly individuals. With an increasing incidence and a high failure rate for pharmaceutical options that are merely symptom-targeting and supportive with many side effects, there is an urgent need for alternative strategies. Despite extensive knowledge on the molecular basis of AD, progress concerning effective disease-modifying therapies has proven to be a challenge. The ability of the CRISPR-Cas9 gene editing system to help identify target molecules or to generate new preclinical disease models could shed light on the pathogenesis of AD and provide promising therapeutic possibilities. Here, we sought to highlight the current understanding of the involvement of the A673T mutation in amyloid pathology, focusing on its roles in protective mechanisms against AD, in relation to the recent status of available therapeutic editing tools.

Self-Medication in Rural Northeastern Romania: Patients' Attitudes and Habits.

In recent years, many healthcare systems, along with healthcare professionals, have provided services in a patient-centered manner, in which patients are key actors in the care process. Encouraging self-care creates responsible patients, but it must be practiced responsibly. This study aims to analyze the tendency towards self-medication for patients from a rural area in Northeastern Romania. Data were collected using a questionnaire, which consisted of 25 questions, that has been developed by the research team. Student's T test or one-way ANOVA was used, and the reliability of the questionnaire was calculated using Cronbach's alpha coefficient. Fifty-eight patients agreed to participate and were interviewed. The results of the study suggest that respondents practice self-medication, which they resort to when their condition cannot be treated with natural remedies or herbs and when it impairs their ability to do their daily activities. Self-medication could be explained by the lack of self-care services as well as the trust patients have in the specific treatment. Patients prefer asking the pharmacist for drugs instead of visiting a physician, which could be due to higher accessibility and time-efficiency, while also being prone to stock up on certain medications due to limited access to healthcare.

Endocannabinoid Modulation in Neurodegenerative Diseases: In Pursuit of Certainty.

Neurodegenerative diseases are an increasing cause of global morbidity and mortality. They occur in the central nervous system (CNS) and lead to functional and mental impairment due to loss of neurons. Recent evidence highlights the link between neurodegenerative and inflammatory diseases of the CNS. These are typically associated with several neurological disorders. These diseases have fundamental differences regarding their underlying physiology and clinical manifestations, although there are aspects that overlap. The endocannabinoid system (ECS) is comprised of receptors (type-1 (CB1R) and type-2 (CB2R) cannabinoid-receptors, as well as transient receptor potential vanilloid 1 (TRPV1)), endogenous ligands and enzymes that synthesize and degrade endocannabinoids (ECBs). Recent studies revealed the involvement of the ECS in different pathological aspects of these neurodegenerative disorders. The present review will explore the roles of cannabinoid receptors (CBRs) and pharmacological agents that modulate CBRs or ECS activity with reference to Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD) and multiple sclerosis (MS).

Impact of the Renin-Angiotensin System on the Pathogeny and Pharmacotherapeutics of Neurodegenerative Diseases.

Brain neurodegenerative diseases (BND) are debilitating conditions that are especially characteristic of a certain period of life and considered major threats to human health. Current treatments are limited, meaning that there is a challenge in developing new options that can efficiently tackle the different components and pathophysiological processes of these conditions. The renin-angiotensin-aldosterone system (RAS) is an endocrine axis with important peripheral physiological functions such as blood pressure and cardiovascular homeostasis, as well as water and sodium balance and systemic vascular resistance-functions which are well-documented. However, recent work has highlighted the paracrine and autocrine functions of RAS in different tissues, including the central nervous system (CNS). It is known that RAS hyperactivation has pro-inflammatory and pro-oxidant effects, thus suggesting that its pharmacological modulation could be used in the management of these conditions. The present paper underlines the involvement of RAS and its components in the pathophysiology of BNDs such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), Huntington's disease (HD), motor neuron disease (MND), and prion disease (PRD), as well as the identification of drugs and pharmacologically active substances that act upon RAS, which could alleviate their symptomatology or evolution, and thus, contribute to novel therapeutic approaches.

Valorization of cricket, Acheta domesticus (Linnaeus, 1758), flour as a source of dietary protein in Japanese quail, Coturnix japonica (Temminck and Schlegel, 1849), farming.

Objective: Quail production is ranked as an important alternative animal protein source in Cameroon. One of the main constraints of this production is the quality of feed, which lacks protein that is regularly supplied by fish meal. To avoid disagreements due to the constant shortage of fish meal, alternative protein sources are needed, and among them are crickets (Acheta domesticus). The goal of this study was to find out how well Japanese quails could be raised if fish meal was replaced with cricket meal. Materials and Methods: A total of 192, 4-week-old quails were divided into 12 similar sets of 8 females and 8 males. The Four experimental diets (T00, T15, T30, and T45) were all formulated based on the level (0%, 15%, 30%, and 45%, respectively) of fish meal substitution with cricket meal in the basal diet (crude protein: 20.18% and ME: 3,013.78 kcal/kg) and randomly assigned to three sets in a completely randomized design consisting of four treatments each repeated three times. Growth, carcass, and some reproduction parameters were collected. The data were analyzed using one-way analysis of variance and the Duncan test, with a significance level of 5%. Results: Cricket meal diets increased body weight in males (204.32 ± 5.69 gm for T45) and regardless of the sex (226.72 ± 29.45 gm for T30) compared to 184.17 ± 3.11 gm and 214.55 ± 32.77 gm for the control group, respectively. In females, substitution at 30% increased body weight (253.80 ± 6.48 gm), while 45% induced a reduction (216.67 ± 6.49 gm) when compared to the control group value (244.92 ± 6.07 gm). Carcass yield and the proportion of different parts were not significantly affected by the experimental diets. Liver proportions were significantly higher at 15% and 35% cricket meal incorporation compared to 45%. First songs and egg laying were recorded at 7 weeks with T15, which also led to improved egg laying performance compared to the other treatments. Ovaries were poorly developed in the T45 females compared to the other treatments. Conclusions: Cricket flour might be a good candidate as a locally available protein source to substitute fish meal in the Japanese quail's diet at the finisher and reproductive stages, and the level of 30% seems to be more efficient.

Systemic Actions of SGLT2 Inhibition on Chronic mTOR Activation as a Shared Pathogenic Mechanism between Alzheimer's Disease and Diabetes.

Alzheimer's disease (AD) affects tens of millions of people worldwide. Despite the advances in understanding the disease, there is an increased urgency for pharmacological approaches able of impacting its onset and progression. With a multifactorial nature, high incidence and prevalence in later years of life, there is growing evidence highlighting a relationship between metabolic dysfunction related to diabetes and subject's susceptibility to develop AD. The link seems so solid that sometimes AD and type 3 diabetes are used interchangeably. A candidate for a shared pathogenic mechanism linking these conditions is chronically-activated mechanistic target of rapamycin (mTOR). Chronic activation of unrestrained mTOR could be responsible for sustaining metabolic dysfunction that causes the breakdown of the blood-brain barrier, tau hyperphosphorylation and senile plaques formation in AD. It has been suggested that inhibition of sodium glucose cotransporter 2 (SGLT2) mediated by constant glucose loss, may restore mTOR cycle via nutrient-driven, preventing or even decreasing the AD progression. Currently, there is an unmet need for further research insight into molecular mechanisms that drive the onset and AD advancement as well as an increase in efforts to expand the testing of potential therapeutic strategies aimed to counteract disease progression in order to structure effective therapies.

Clinical and pathological considerations in lumbar herniated disc associated with inflammatory lesions.

Lumbar herniated disc is the most frequent cause for lumbar pain. It is caused by degenerative, macroscopic and microscopic changes of the intervertebral discs. It is a chronic disease, with periods of exacerbation and remission under drug and physiotherapeutic treatment. When the disc lesions are large, with intense symptoms, reduced or impossible movements, with pain radiating to the sciatic nerve trajectory, a surgical treatment is required, to remove the herniated nucleus pulposus and decompress the nerve roots. Patients who present high inflammatory signs, high inflammatory serous markers, may have a longer postoperative recovery period, while the motor recovery may be late and incomplete. We analyzed a group of 24 patients with lumbar herniated disc that required discectomy, with clear inflammatory signs, together with histopathological and immunohistochemical changes present in the herniated disc.

Link Between Diabetes and Alzheimer's Disease due to the Shared Amyloid Aggregation and Deposition Involving both Neurodegenerative Changes and Neurovascular Damages.

Diabetes and Alzheimer's disease are two highly prevalent diseases among the aging population and have become major public health concerns in the 21st century, with a significant risk to each other. Both of these diseases are increasingly recognized to be multifactorial conditions. The terms "diabetes type 3" or "brain diabetes" have been proposed in recent years to provide a complete view of the potential common pathogenic mechanisms between these diseases. While insulin resistance or deficiency remains the salient hallmarks of diabetes, cognitive decline and non-cognitive abnormalities such as impairments in visuospatial function, attention, cognitive flexibility, and psychomotor speed are also present. Furthermore, amyloid aggregation and deposition may also be drivers for diabetes pathology. Here, we offer a brief appraisal of social impact and economic burden of these chronic diseases and provide insight into amyloidogenesis through considering recent advances of amyloid-ß aggregates on diabetes pathology and islet amyloid polypeptide on Alzheimer's disease. Exploring the detailed knowledge of molecular interaction between these two amyloidogenic proteins opens new opportunities for therapies and biomarker development.

Impact of Alpha-Lipoic Acid Chronic Discontinuous Treatment in Cardiometabolic Disorders and Oxidative Stress Induced by Fructose Intake in Rats.

Insulin resistance (IR) and cardiometabolic disorders are the main consequences of today's alimentary behavior. This study evaluates the effects of a chronic-discontinuous treatment with alpha-lipoic acid (AL), an antioxidant substance that improves glycemic control associated with diabetes mellitus, on metabolic disorders and plasma oxidative stress induced by fructose intake, in rats. Sprague-Dawley rats (48 animals) were randomized into two series (n = 24): rats fed with standard chow or with standard chow supplemented with 60% fructose. In each of the two series, for 2 weeks/month over 12 weeks, a group of rats (n = 12) was intraperitoneally injected with NaCl 0.9%, and a second group (n = 12) received AL 50mg/kg/day. Body weight, glycemia, and systolic blood pressure were monitored throughout the study. After 12 weeks, IR, plasma lipoproteins, uric acid, transaminase activities, and oxidative stress markers were assessed. The high fructose-enriched diet induced cardiometabolic disorders (hypertension, hyperglycemia, IR and dyslipidemia), an increase in uric acid concentration, transaminase activities and C-reactive protein level. This diet also enhanced plasma products of lipid and protein oxidation, homocysteine level, and decreased GSH/GSSG ratio. In this field, there is evidence to indicate that oxidative stress plays an important role in the etiology of diabetic complications. AL discontinuous treatment prevents the metabolic disorders induced by fructose intake, reduced plasma lipid and protein oxidation-products, and restored the GHS/GSSG ratio. Our study proves a promising potential of the chronic-discontinuous treatment of AL and highlights the pleiotropic effects of this antioxidant substance in metabolic disorders such as diabetes.

A Comparative Study on the Memory-Enhancing Actions of Oral Renin-Angiotensin System Altering Drugs in Scopolamine-Treated Mice.

This study was designed to evaluate the spatial working memory (as studied in Y-maze) or short-term and long-term spatial memory (assessed in radial 8 arms-maze task), in a scopolamine-induced memory deficits model in mice, by the oral administration of 2 angiotensin-converting enzyme inhibitors-captopril and ramipril and also the effects of the AT1 receptor antagonist, losartan. The present article was initiated as a reaction to the clinical setting of hypertensive disease, which involves lifelong administration of antihypertensive drugs, dietary or lifestyle constraints, and aging, which all take a toll on the higher functions of the nervous system. Most of the patients with cognitive decline suffer of various metabolic imbalances, hypertension, cardiac and kidney disease, many of them which are treated with oral administration of Renin-angiotensin aldosterone system-altering agents like those presented above. Our results showed a protective effect of captopril, ramipril, and losartan prescopolamine administration on spontaneous alternation in Y-maze task, as compared to scopolamine-alone treated mice, as well as decreased number of working memory errors and reference memory errors in radial-arm maze for both losartan + scopolamine and ramipril + scopolamine groups versus scopolamine alone. This could have a therapeutical relevance, especially since oral administration was preferred in our report, as it is used in the therapeutic procedures in humans, further enhancing the similarities with the clinical conditions.

Alzheimer's Disease Pharmacotherapy in Relation to Cholinergic System Involvement.

Alzheimer's disease, a major and increasing global health challenge, is an irreversible, progressive form of dementia, associated with an ongoing decline of brain functioning. The etiology of this disease is not completely understood, and no safe and effective anti-Alzheimer's disease drug to prevent, stop, or reverse its evolution is currently available. Current pharmacotherapy concentrated on drugs that aimed to improve the cerebral acetylcholine levels by facilitating cholinergic neurotransmission through inhibiting cholinesterase. These compounds, recognized as cholinesterase inhibitors, offer a viable target across key sign domains of Alzheimer's disease, but have a modest influence on improving the progression of this condition. In this paper, we sought to highlight the current understanding of the cholinergic system involvement in Alzheimer's disease progression in relation to the recent status of the available cholinesterase inhibitors as effective therapeutics.