Autophagy dysfunction in Alzheimer’s disease: Biochemistry and therapeutic future

 

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Autores: Serrano-Monge, Ariana, Álvarez-Brenes, Daniel, Calderón-Blanco, Isaac, Jiménez-Murillo, Sofía, Montoya-Mata, Raquel
Formato: artículo original
Estado:Versión publicada
Fecha de Publicación:2025
Descripción:Alzheimer’s Disease (AD), which is the leading cause of dementia, is characterized by the accumulation of β-amyloid and neurofibrillary tangles, which cause cognitive impairment. In Latin America and the Caribbean, AD represents between 50% and 84% of dementia cases, with projections indicating an increase to 13.7 million cases by 2050. The process of cellular autophagy, a vital process that maintains homeostasis by degrading damaged cells, is essential for neuronal health. Autophagy dysfunction is related to the accumulation of misfolded proteins in AD. Although autophagy is initially activated as a protective response against β-amyloid, its accumulation blocks lysosomal degradation, resulting in the formation of neurotoxic oligomers and amyloid plaques, causing inflammation and neuronal damage. Alterations in key proteins such as Beclin 1, PICALM and PSEN-1 aggravate Aβ accumulation, affecting ATP production and contributing to neurodegeneration. The effectiveness of current treatments remains a subject of debate within the scientific community due to their limitations, including the difficulty in replicating the human disease in animal models, insufficient penetration into the central nervous system, and potential adverse effects. Therefore, its therapeutic future focuses primarily on expanding clinical trials by studying different pathological pathways and targeting biomarkers for early disease detection.
País:Portal de Revistas TEC
Institución:Instituto Tecnológico de Costa Rica
Repositorio:Portal de Revistas TEC
Lenguaje:Español
OAI Identifier:oai:ojs.pkp.sfu.ca:article/7589
Acceso en línea:https://revistas.tec.ac.cr/index.php/tec_marcha/article/view/7589
Palabra clave:Neuronas
enfermedad de Alzheimer
β-amiloide
autofagosomas
LC3
Neurons
Alzheimer’s disease
β-amyloid
autophagosomes