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Review
. 2021;19(5):679-692.
doi: 10.2174/1570159X18666200807130637.

Neurodegenerative Pathways in Alzheimer's Disease: A Review

Anu Kunnath Ramachandran  1 , Subham Das  1 , Alex Joseph  1 , Gurupur Gautham Shenoy  1 , Angel Treasa Alex  2 , Jayesh Mudgal  3
Affiliations
Review

Neurodegenerative Pathways in Alzheimer's Disease: A Review

Anu Kunnath Ramachandran et al. Curr Neuropharmacol. 2021.

Abstract

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 3β, 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.

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

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Figures

Fig. (1)
Fig. (1)
Major hypotheses behind AD.
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Cholinergic hypothesis of neurodegeneration.
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Amyloidogenic pathway of APP.
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Tau proteins and AD.
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Role of NMDA in AD.
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ApoE and Aβ plaque formation.
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Relation of Wnt signaling pathway with AD.
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Role of sirtuins in AD.
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mTOR in AD.
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Activity of caspases in AD.
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Role of autophagy in Alzheimer’s.
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PUFA and AD.
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Calcium in AD.
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Activity of ceramides in Alzheimer’s brain.
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Notch signaling in the progression of AD.
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Neurotrophins in AD.
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JNK and AD.
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Fig. (18)
Role of GSK3β in the progression of AD.
See this image and copyright information in PMC

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