APP dyshomeostasis in the pathogenesis of Alzheimer's disease : implications for current drug targets
Sirisi, S. (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Sánchez-Aced, É. (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Belbin, Olivia (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Lleó, Alberto (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona

Fecha:	2024
Resumen:	The Amyloid precursor protein (APP) is a transmembrane glycoprotein from which amyloid-β (Aβ) peptides are generated after proteolytic cleavage. Aβ peptides are the main constituent of amyloid plaques in Alzheimer's Disease (AD). The physiological functions of APP in the human adult brain are very diverse including intracellular signaling, synaptic and neuronal plasticity, and cell adhesion, among others. There is growing evidence that APP becomes dysfunctional in AD and that this dyshomeostasis may impact several APP functions beyond Aβ generation. The vast majority of current anti-amyloid approaches in AD have focused on reducing the synthesis of Aβ or increasing the clearance of brain Aβ aggregates following a paradigm in which Aβ plays a solo in APP dyshomeostasis. A wider view places APP at the center stage in which Aβ is an important, but not the only, factor involved in APP dyshomeostasis. Under this paradigm, APP dysfunction is universal in AD, but with some differences across different subtypes. Little is known about how to approach APP dysfunction therapeutically beyond anti-Aβ strategies. In this review, we will describe the role of APP dyshomeostasis in AD beyond Aβ and the potential therapeutic strategies targeting APP.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article de revisió ; recerca ; Versió publicada
Materia:	APP ; Alzheimer's disease ; Down syndrome ; Drug ; Therapeutic targets
Publicado en:	Alzheimer's research & therapy, Vol. 16 Núm. 1 (december 2024) , p. 144, ISSN 1758-9193

DOI: 10.1186/s13195-024-01504-w
PMID: 38951839

7 p, 1.7 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Recerca Sant Pau
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