Innovative pathological network-based multitarget approaches for Alzheimer's disease treatment

Alzheimer's disease (AD) is an age‐associated neurodegenerative disorder, characterized by memory loss, retardation of thinking and reasoning, progressive cognitive impairment, and changes in personality and behaviors.1 AD is the most frequent cause of dementia, accounting for 60%–80% of all ca...

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Detalles Bibliográficos
Autores: Mayo, Paloma, Pascual, Jorge, Crisman, Enrique, Domínguez, Cristina, López, Manuela G., León, Rafael
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/360459
Acceso en línea:http://hdl.handle.net/10261/360459
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
drug targets combinations
multifactorial disease
multitarget‐directed ligands
multitarget drugs
polypharmacology drug
Descripción
Sumario:Alzheimer's disease (AD) is an age‐associated neurodegenerative disorder, characterized by memory loss, retardation of thinking and reasoning, progressive cognitive impairment, and changes in personality and behaviors.1 AD is the most frequent cause of dementia, accounting for 60%–80% of all cases. 2 In 2022, AD affected over 55 million people around the world being the seventh leading cause of mortality and morbidity, a figure that will increase to 152 million by 2050,3 with an estimation of 10 million new cases each year and a projected healthcare expenditure of around US $1.1 trillion in the United States. 4 AD incidence increases dramatically with age, being 5% of people aged 65–74 years, 13% of people aged 75–84 years, and 33% of people aged 85 years or older.5 Although several genetic predisposition factors have been described, only 5% of cases are familiar or early‐onset, while 95% of the cases are sporadic or late‐onset (LOAD). To date, the causes driving LOAD onset and development remain elusive; however, different pathological pathways have been implicated, including aberrant protein aggregation, mitochondrial dysfunction, OS, calcium ion (Ca2+ ) dyshomeostasis, chronic neuroinflammation, and autophagy failure, among others. The progressive increase in LOAD cases, together with the fact that there is still no effective treatment, highlights the urgent need to find effective drugs