Current Drug Targets in Alzheimer's Associated Memory Impairment: A Comprehensive Review

Anna Mathew, Vignesh Balaji E, Sreedhara Ranganath K. Pai, Anoop Kishore, Vasudev Pai, Ramadevi Pemmireddy, Chandrashekar K S

Research output: Contribution to journalReview articlepeer-review

Abstract

Alzheimer's disease (AD) is the most prevalent form of dementia among geriatrics. It is a progressive, degenerative neurologic disorder that causes memory and cognition loss. The accumulation of amyloid fibrils and neurofibrillary tangles in the brain of AD patients is a distinguishing feature of the disease. Therefore, most of the current therapeutic goals are targeting inhibition of beta-amyloid synthesis and aggregation as well as tau phosphorylation and aggregation. There is also a loss of the cholinergic neurons in the basal forebrain, and first-generation therapeutic agents were primarily focused on compensating for this loss of neurons. However, cholinesterase inhibitors can only alleviate cognitive symptoms of AD and cannot reduce the progression of the disease. Understanding the molecular and cellular changes associated with AD pathology has advanced significantly in recent decades. The etiology of AD is complex, with a substantial portion of sporadic AD emerging from unknown reasons and a lesser proportion of early-onset familial AD (FAD) caused by a mutation in several genes, such as the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2) genes. Hence, efforts are being made to discover novel strategies for these targets for AD therapy. A new generation of AChE and BChE inhibitors is currently being explored and evaluated in human clinical trials for AD symptomatic treatment. Other approaches for slowing the progression of AD include serotonergic modulation, H3 receptor antagonism, phosphodiesterase, COX-2, and MAO-B inhibition. The present review provides an insight into the possible therapeutic strategies and their molecular mechanisms, enlightening the perception of classical and future treatment approaches.

Original languageEnglish
Pages (from-to)255-275
Number of pages21
JournalCNS & neurological disorders drug targets
Volume22
Issue number2
DOIs
Publication statusPublished - 02-2023

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Pharmacology

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