The Pathogenesis in Alzheimer's Disease: TREM2 as a Potential Target.
J Integr Neurosci
; 22(6): 150, 2023 Oct 30.
Article
en En
| MEDLINE
| ID: mdl-38176932
ABSTRACT
Alzheimer's disease (AD) is ranked as the third-most expensive illness and sixth leading cause of mortality. It is associated with the deposition of extracellular amyloid-ß (Aß) in neural plaques (NPs), as well as intracellular hyperphosphorylated tau proteins that form neurofibrillary tangles (NFTs). As a new target in regulating neuroinflammation in AD, triggering receptor expressed on myeloid cells 2 (TREM2) is highly and exclusively expressed on the microglial surface. TREM2 interacts with adaptor protein DAP12 to initiate signal pathways that mainly dominant microglia phenotype and phagocytosis mobility. Furthermore, TREM2 gene mutations confer increased AD risk, and TREM2 deficiency exhibits more dendritic spine loss around neural plaques. Mechanisms for regulating TREM2 to alleviate AD has evolved as an area of AD research in recent years. Current medications targeting Aß or tau proteins are unable to reverse AD progression. Emerging evidence implicating neuroinflammation may provide novel insights, as early microglia-related inflammation can be induced decades prior to the commencement of AD-related cognitive damage. Physical exercise can exert a neuroprotective effect over the course of AD progression. This review aims to (1) summarize the pathogenesis of AD and recent updates in the field, (2) assess the concept that AD cognitive impairment is closely correlated with microglia-related inflammation, and (3) review TREM2 functions and its role between exercise and AD, which is likely to be an ideal candidate target.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Alzheimer
Tipo de estudio:
Etiology_studies
Límite:
Humans
Idioma:
En
Revista:
J Integr Neurosci
Asunto de la revista:
NEUROLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Singapur