Issue 46, 2022

Multipronged diagnostic and therapeutic strategies for Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and a major contributor to dementia cases worldwide. AD is clinically characterized by learning, memory, and cognitive deficits. The accumulation of extracellular amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs) of tau are the pathological hallmarks of AD and are explored as targets for clinical diagnosis and therapy. AD pathology is poorly understood and there are no fully approved diagnosis and treatments. Notwithstanding the gap, decades of research in understanding disease mechanisms have revealed the multifactorial nature of AD. As a result, multipronged and holistic approaches are pertinent to targeting multiple biomarkers and targets for developing effective diagnosis and therapeutics. In this perspective, recent developments in Aβ and tau targeted diagnostic and therapeutic tools are discussed. Novel indirect, combination, and circulating biomarkers as potential diagnostic targets are highlighted. We underline the importance of multiplexing and multimodal detection of multiple biomarkers to generate biomarker fingerprints as a reliable diagnostic strategy. The classical therapeutics targeting Aβ and tau aggregation pathways are described with bottlenecks in the strategy. Drug discovery efforts targeting multifaceted toxicity involving protein aggregation, metal toxicity, oxidative stress, mitochondrial damage, and neuroinflammation are highlighted. Recent efforts focused on multipronged strategies to rationally design multifunctional modulators targeting multiple pathological factors are presented as future drug development strategies to discover potential therapeutics for AD.

Graphical abstract: Multipronged diagnostic and therapeutic strategies for Alzheimer's disease

Article information

Article type
Perspective
Submitted
14 7月 2022
Accepted
13 10月 2022
First published
14 10月 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022,13, 13657-13689

Multipronged diagnostic and therapeutic strategies for Alzheimer's disease

M. Ramesh and T. Govindaraju, Chem. Sci., 2022, 13, 13657 DOI: 10.1039/D2SC03932J

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