Targeting Abnormal Tau Phosphorylation for Alzheimer ’s Therapeutics
Horm Metab Res DOI: 10.1055/a-2238-1384Alzheimer’s disease (AD) is a widespread neurodegenerative disorder
characterized by progressive memory and cognitive decline, posing a formidable
public health challenge. This review explores the intricate interplay between
two pivotal players in AD pathogenesis: β-amyloid (Aβ) and tau
protein. While the amyloid cascade theory has long dominated AD research, recent
developments have ignited debates about its centrality. Aβ plaques and
tau NFTs are hallmark pathologies in AD. Aducanumab and lecanemab, monoclonal
antibodies targeting Aβ, have been approved, albeit amidst controversy,
raising questions about the therapeutic efficacy of Aβ-focused
interventions. On the other hand, tau, specifically its hyperphosphorylation,
disrupts microtubule stability and contributes to neuronal dysfunction. Various
post-translational modifications of tau drive its aggregation into NFTs.
Emerging treatments targeting tau, such as GSK-3β and CDK5 inhibitors,
have shown promise in preclinical and clinical studies. Restoring the
equilibrium between protein kinases and phosphatases, notably protein
phosphatase-2A (PP2A), is a promising avenue for AD therapy, as tau is primarily
regulated by its phosphorylation state. Activation of tau-specific phosphatases
offers potential for mitiga...
Source: Hormone and Metabolic Research - Category: Endocrinology Authors: Singh, Aditya Ansari, Vaseem Ahamad Mahmood, Tarique Hasan, Syed Misbahul Wasim, Rufaida Maheshwari, Shubhrat Akhtar, Juber Sheikh, Suvaiv Vishwakarma, Vishal Kumar Tags: Review Source Type: research
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