"Current and emerging drug therapies in Alzheimer's disease: A pathophysiological Perspective"

Neuroscience. 2025 Jan 26:565:499-518. doi: 10.1016/j.neuroscience.2024.11.078. Epub 2024 Dec 9.

Abstract

The analytical and experimental investigation of several targets and biomarkers that help in explaining significant cognitive deficits, covering drug development and precision medicine aimed at different chronic neurodegenerative conditions such as Alzheimer's disease (AD), Parkinson's disease, synaptic dysfunction, brain damage from neuronal apoptosis, and other disease pathologies; this served as the foundation for all phase studies. The focus of current therapeutic approaches is on developing humanized antibodies, agonist and antagonist drugs, receptors, signaling molecules, major targeted drug-metabolizing enzymes, and other metabolites to treat neurodegeneration in the AD brain brought on by tau hyperphosphorylation, amyloid plagues, or other cholinergic effects. The five A's-amnesia, agnosia, aphasia, apraxia, and anomia-are the typical symptoms associated with AD. While the main goal of drug therapeutics studies is modified amino acids acting as pro-drugs, pharmacokinetics studies and trends in evaluating drug-drug interactions focus on interactions between drugs and antibodies, drugs and therapeutic biologics like metabolites, herbs, interleukin-based, and gene silencing mechanism-based. Studies on the biotransformation of xenobiotic compounds and the metabolism of exogenous and endogenous substances are conducted under Phase I, Phase II, and Phase III trials because the pivotal pharmacokinetic properties of drugs, such as absorption, distribution, metabolism, and excretion (ADME), aid in understanding variations in the crucial improvement of various target drugs. This review also highlights the developments in soon-to-be genetically created targeted medications that may serve as ground-breaking treatments for cholinergic illnesses in the brains of AD patients and other neurodegenerative conditions.

Keywords: Alzheimer’s disease; Emerging drugs; Neurodegeneration; Phase study; Physiopathalogy.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Animals
  • Drug Development / methods
  • Humans