DAMAGE TO MITOCHONDRIAL AND ENDOPLASMIC RETICULUM STRESS RESPONSE SYSTEMS AND THE GENERATION OF DEGENERATIVE DISEASES: A SCOPUS REVIEW

Fonseca-de-Souza A. L.*, Santos L. S., Moreira de Carvalho G.O.A. and Fortes F. S. A.

ABSTRACT

The maintenance of protein homeostasis is essential for neuronal health, and the failure of these mechanisms leads to the accumulation of misfolded proteins, such as α-synuclein, tau and Aβ, which form toxic aggregates, associated with diseases such as Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis (ALS) and Huntington's. Protein balance is maintained by a complex network of molecular mechanisms, including chaperones, ubiquitin- proteasome system, autophagy, cellular stress response pathways that ensure the correct folding, degradation and elimination of defective proteins. However, factors such as mutations, environmental and metabolic stress can disrupt this network, in addition to aging, which reduces its effectiveness and performance, resulting in the formation of toxic protein aggregates. This systematic review reinforces the relevance of proteostasis in neuronal health and in the development of neurodegenerative diseases, suggesting that precise modulation of these pathways may be an effective therapeutic approach to slow the progression of these conditions. The work developed is an exploratory study, carried out through a bibliographic research. A literature search was carried out in the Medline, Elsevier, Lilacs and Capes databases of periodicals, published between 2014 and 2024. The selected studies underwent an evaluation of the eligibility criteria. The mechanisms of a proteostasis network were presented in detail and the understanding of these processes reveals new possibilities for treatment of neurodegenerative diseases, opening new perspectives for therapeutic interventions aimed at preserving proteostasis and, consequently, preventing these diseases.

Keywords: Proteostasis, UPRMT, UPRER, neurodegeneration