Comprehensive Review on Alzheimer’s Disease: Causes and Treatment

Molecules, Journal Year: 2020, Volume and Issue: 25(24), P. 5789 - 5789

Published: Dec. 8, 2020

Alzheimer’s disease (AD) is a disorder that causes degeneration of the cells in brain and it main cause dementia, which characterized by decline thinking independence personal daily activities. AD considered multifactorial disease: two hypotheses were proposed as for AD, cholinergic amyloid hypotheses. Additionally, several risk factors such increasing age, genetic factors, head injuries, vascular diseases, infections, environmental play role disease. Currently, there are only classes approved drugs to treat including inhibitors cholinesterase enzyme antagonists N-methyl d-aspartate (NMDA), effective treating symptoms but do not cure or prevent Nowadays, research focusing on understanding pathology targeting mechanisms, abnormal tau protein metabolism, β-amyloid, inflammatory response, free radical damage, aiming develop successful treatments capable stopping modifying course AD. This review discusses currently available future theories development new therapies disease-modifying therapeutics (DMT), chaperones, natural compounds.

Language: Английский

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A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1851 - 1851

Published: Feb. 6, 2022

Neurodegenerative disorders are primarily characterized by neuron loss. The most common neurodegenerative include Alzheimer’s and Parkinson’s disease. Although there several medicines currently approved for managing disorders, a large majority of them only help with associated symptoms. This lack pathogenesis-targeting therapies is due to the restrictive effects blood–brain barrier (BBB), which keeps close 99% all “foreign substances” out brain. Since their discovery, nanoparticles have been successfully used targeted delivery into many organs, including review briefly describes pathophysiology Alzheimer’s, disease, amyotrophic lateral sclerosis, current management approaches. We then highlight major challenges brain-drug delivery, followed role nanotherapeutics diagnosis treatment various neurological disorders.

Language: Английский

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Alzheimer’s disease and its treatment by different approaches: A review

European Journal of Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 216, P. 113320 - 113320

Published: Feb. 23, 2021

Language: Английский

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Synaptic degeneration in Alzheimer disease

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 19(1), P. 19 - 38

Published: Dec. 13, 2022

Language: Английский

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Synaptic dysfunction in Alzheimer's disease: Mechanisms and therapeutic strategies

Pharmacology & Therapeutics, Journal Year: 2018, Volume and Issue: 195, P. 186 - 198

Published: Nov. 12, 2018

Language: Английский

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Glymphatic system, AQP4, and their implications in Alzheimer’s disease

Neurological Research and Practice, Journal Year: 2021, Volume and Issue: 3(1)

Published: Jan. 19, 2021

Abstract Lacking conventional lymphatic system, the central nervous system requires alternative clearance systems, such as glymphatic which promotes of interstitial solutes. Aquaporin-4 water channels (AQP4) are an integral part this and related to neuropathologies, Alzheimer’s disease (AD). The associated proteins amyloid β tau is diminished by impairment, due lack AQP4. Even though AQP4 mislocalisation (which affects its activity) a phenotype AD, it remains controversial topic, still unclear if phenotype-promoting factor or consequence pathology. This review provides important updated knowledge about itself, their link with disease. Finally, therapeutic target proposed ameliorate Disease other neuropathologies AQP4-related.

Language: Английский

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ESO Guideline on covert cerebral small vessel disease

European Stroke Journal, Journal Year: 2021, Volume and Issue: 6(2), P. CXI - CLXII

Published: May 11, 2021

‘Covert’ cerebral small vessel disease (ccSVD) is common on neuroimaging in persons without overt neurological manifestations, and increases the risk of future stroke, cognitive impairment, dependency, death. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist with clinical decisions about management ccSVD, specifically white matter hyperintensities lacunes, prevent adverse outcomes. The were developed according ESO standard operating procedures Grading Recommendations, Assessment, Development, Evaluation (GRADE) methodology. We prioritised outcomes decline or dementia, death, mobility mood disorders, interventions blood pressure lowering, antiplatelet drugs, lipid lifestyle modifications, glucose lowering conventional treatments for dementia. systematically reviewed literature, assessed evidence, formulated where feasible, expert consensus statements. found little direct mostly low quality. recommend patients ccSVD hypertension have their well controlled; lower targets may reduce progression. do not drugs such as aspirin ccSVD. evidence Smoking cessation a health priority. regular exercise which benefit cognition, healthy diet, good sleep habits, avoiding obesity stress general reasons. In we no control absence diabetes Alzheimer dementia treatments. Randomised controlled trials endpoints are priority

Language: Английский

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The synapse as a treatment avenue for Alzheimer’s Disease

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(7), P. 2940 - 2949

Published: April 20, 2022

Language: Английский

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Extrasynaptic NMDA receptors in acute and chronic excitotoxicity: implications for preventive treatments of ischemic stroke and late-onset Alzheimer’s disease

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: July 3, 2023

Abstract Stroke and late-onset Alzheimer’s disease (AD) are risk factors for each other; the comorbidity of these brain disorders in aging individuals represents a significant challenge basic research clinical practice. The similarities differences between stroke AD terms pathogenesis pathophysiology, however, have rarely been comparably reviewed. Here, we discuss background recent progresses that important informative related dementia (ADRD). Glutamatergic NMDA receptor (NMDAR) activity NMDAR-mediated Ca 2+ influx essential neuronal function cell survival. An ischemic insult, can cause rapid increases glutamate concentration excessive activation NMDARs, leading to swift overload cells acute excitotoxicity within hours days. On other hand, mild upregulation NMDAR activity, commonly seen animal models patients, is not immediately cytotoxic. Sustained hyperactivity dysregulation lasting from months years, nevertheless, be pathogenic slowly evolving events, i.e. degenerative excitotoxicity, development AD/ADRD. Specifically, mediated by extrasynaptic NMDARs (eNMDARs) downstream pathway transient potential cation channel subfamily M member (TRPM) primarily responsible excitotoxicity. subunit GluN3A plays “gatekeeper” role neuroprotective against both chronic Thus, share an NMDAR- -mediated mechanism provides common target preventive possibly disease-modifying therapies. Memantine (MEM) preferentially blocks eNMDARs was approved Federal Drug Administration (FDA) symptomatic treatment moderate-to-severe with variable efficacy. According eNMDARs, it conceivable MEM eNMDAR antagonists should administered much earlier, preferably during presymptomatic phases This anti-AD could simultaneously serve as preconditioning strategy attacks ≥ 50% patients. Future on regulation enduring control homeostasis, events will provide promising opportunity understand treat AD/ADRD stroke.

Language: Английский

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Alzheimer’s disease and its treatment–yesterday, today, and tomorrow

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: May 24, 2024

Alois Alzheimer described the first patient with Alzheimer’s disease (AD) in 1907 and today AD is most frequently diagnosed of dementias. a multi-factorial neurodegenerative disorder familial, life style comorbidity influences impacting global population more than 47 million projected escalation by 2050 to exceed 130 million. In USA demographic encompasses approximately six individuals, expected increase surpass 13 2050, antecedent phase AD, recognized as mild cognitive impairment (MCI), involves nearly 12 individuals. The economic outlay for management AD-related decline estimated at 355 billion USD. addition, intensifying prevalence cases countries modest intermediate income further enhances urgency therapeutically cost-effective treatments improving quality patients their families. This narrative review evaluates pathophysiological basis an initial focus on therapeutic efficacy limitations existing drugs that provide symptomatic relief: acetylcholinesterase inhibitors (AChEI) donepezil, galantamine, rivastigmine, N-methyl-D-aspartate receptor (NMDA) allosteric modulator, memantine. hypothesis amyloid-β (Aβ) tau are appropriate targets have potential halt progress critically analyzed particular clinical trial data anti-Aβ monoclonal antibodies (MABs), namely, aducanumab, lecanemab donanemab. challenges dogma targeting Aβ will benefit majority subjects MABs unlikely be “magic bullet”. A comparison benefits disadvantages different classes forms determining new directions research alternative drug undergoing pre-clinical assessments. we discuss stress importance treatment co-morbidities, including hypertension, diabetes, obesity depression known risk developing AD.

Language: Английский

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