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Neurodegenerative Pathways in Alzheimer's Disease: A Review

Journal

CURRENT NEUROPHARMACOLOGY
Volume 19, Issue 5, Pages 679-692

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1570159X18666200807130637

Keywords

Alzheimer's disease; neurodegenerative pathways; novel drug targets; acetylcholinesterase; glycogen synthase kinase; notch signaling; apolipoprotein E

Funding

  1. AICTE, New Delhi
  2. Manipal Academy of Higher Education

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Alzheimer's disease is a complex neurodegenerative disorder characterized by memory loss, cognitive decline, and behavioral changes, leading to a low quality of life for patients. The disease involves a variety of neuropathological mechanisms, with no current cure or effective disease-modifying therapies available.
Alzheimer's disease (AD) is a complex neurodegenerative disease that leads to insidious deterioration of brain functions and is considered the sixth leading cause of death in the world. Alzheimer's patients suffer from memory loss, cognitive deficit and behavioral changes; thus, they eventually follow a low-quality life. AD is considered as a multifactorial disorder involving different neuropathological mechanisms. Recent research has identified more than 20 pathological factors that are promoting disease progression. Three significant hypotheses are said to be the root cause of disease pathology, which include acetylcholine deficit, the formation of amyloid-beta senile plaques and tau protein hyperphosphorylation. Apart from these crucial factors, pathological factors such as apolipoprotein E (APOE), glycogen synthase kinase 3 beta, notch signaling pathway, Wnt signaling pathway, etc., are considered to play a role in the advancement of AD and therefore could be used as targets for drug discovery and development. As of today, there is no complete cure or effective disease altering therapies for AD. The current therapy is assuring only symptomatic relief from the disease, and progressive loss of efficacy for these symptomatic treatments warrants the discovery of newer drugs by exploring these novel drug targets. A comprehensive understanding of these therapeutic targets and their neuropathological role in AD is necessary to identify novel molecules for the treatment of AD rationally.

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