BIOLOGICAL MECHANISMS OF AUTOPHAGY IN NEURODEGENERATIVE DISEASES: ROLE OF CELLULAR SIGNALING AND LYSOSOMAL DEGRADATION

Abstract

This study analyzes the biochemical mechanisms of autophagy in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s, focusing on cellular signaling (mTOR/AMPK), mitophagy (PINK1/Parkin), and lysosomal function (TFEB), to elucidate pathogenesis and identify therapeutic targets. An integrative, exploratory, and descriptive literature review with a qualitative approach is conducted using databases like PubMed, SciELO, LILACS, Scopus, and Web of Science, covering studies from 2015 to 2025. Descriptors such as “autophagy,” “mitophagy,” and “neurodegenerative diseases” are combined with Boolean operators. Articles in Portuguese, English, or Spanish, including clinical trials, systematic reviews, experimental, and observational studies, are included, excluding duplicates, irrelevant publications, or non-rigorous works. The analysis categorizes findings into neuronal homeostasis, mitochondrial quality, lysosomal function, and therapeutic implications. It consolidates evidence on autophagic dysfunction, clarifying the “autophagy paradox” and highlighting strategies like mTOR inhibitors and TFEB activators. The study advances pathophysiology understanding and proposes innovative interventions.