DISORDERS OF CHAPERONE ACTION AND THE GENERATION OF DEGENERATIVE DISEASES: A SCOPUS REVIEW

Luana Stephany dos Santos, Gabriella Oliveira Alves Moreira de Carvalho, Fabio da Silva de Azevedo Fortes and André Luiz Fonseca de Souza*

ABSTRACT

Protein homeostasis is essential for neuronal health, and its failure leads to the accumulation of misfolded proteins, such as α-synuclein, tau, huntingtin 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, the ubiquitin-proteasome system, autophagy and 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, which reduces its effectiveness and yield, leading to the production of toxic protein aggregates. This review reinforces the relevance of maintaining chaperone function 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 bibliographic research. A literature search was conducted in the Medline, Elsevier, Lilacs and Capes databases for periodicals published between 2014 and 2024. The selected studies were assessed according to the eligibility criteria. After critical reading of the selected articles, we observed a main relationship between dysfunctions in the function of chaperones, also called heat shock proteins, and the pathophysiology of Amyotrophic Lateral Sclerosis (ALS), an extremely serious disease whose treatment is very difficult due to the scarcity of pharmacological alternatives. Thus, a deep understanding of this relationship brings new possibilities for treatment and/or prevention of neurodegenerative diseases, opening new perspectives for therapeutic interventions aimed at preserving proteostasis.

Keywords: Proteostasis; Heat Shock Proteins (HSP); Neurodegeneration