AUTHOR=Mançano Alquiandra Stefani Ferreira , Pina Juliana Guanaes , Froes Bruna Rojas , Sciani Juliana Mozer 

TITLE=Autophagy-lysosomal pathway impairment and cathepsin dysregulation in Alzheimer’s disease

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1490275

DOI=10.3389/fmolb.2024.1490275

ISSN=2296-889X

ABSTRACT=<p>Alzheimer’s disease (AD) is characterized by neuronal loss, attributed to amyloid-beta (Aβ) aggregation and accumulation. The autophagy-lysosomal pathway, including cathepsins B and D, is crucial for protein degradation and clearance, but it is impaired in some diseases. This review summarizes current knowledge on the dysregulation of this pathway in AD. Accumulating evidence suggests that Aβ overload impairs autophagy-lysosomal function and cathepsin activity, exacerbating Aβ accumulation and neurodegeneration. However, the precise mechanisms underlying these interactions remain elusive. Despite these challenges, targeting the lysosomal pathway emerges as a promising therapeutic strategy, and a comprehensive understanding of the autophagy-lysosomal system is essential to develop effective interventions for AD.</p>