Amyloid Precursor Protein in Central and Peripheral Cholinergic Synaptopathies

Alzheimer´s disease is the most widespread form of dementia in the elderly. One of the characteristics of this disease is the profound functional deficit of the cholinergic system as a consequence of synaptic loss. Amyloid precursor protein (APP) is a type-I transmembrane protein present in brain sy...

ver descrição completa

Detalhes bibliográficos
Autores: Borroni, Maria Virginia, Barrantes, Francisco Jose
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2011
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositório:CONICET Digital (CONICET)
Idioma:inglês
OAI Identifier:oai:ri.conicet.gov.ar:11336/42475
Acesso em linha:http://hdl.handle.net/11336/42475
Access Level:Acceso aberto
Palavra-chave:Amyloid Precursor Protein
Acetylcholine Receptor
Alzheimer Disease
Amyloid Peptide
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descrição
Resumo:Alzheimer´s disease is the most widespread form of dementia in the elderly. One of the characteristics of this disease is the profound functional deficit of the cholinergic system as a consequence of synaptic loss. Amyloid precursor protein (APP) is a type-I transmembrane protein present in brain synapses and at the neuromuscular junction in the peripheral nervous system. It is developmentally regulated and affects synapse formation and cholinergic transmission. Misprocessing of APP leads to the generation of a highly fibrillogenic peptide, amyloid beta (Aβ), which aggregates and forms amyloid plaques, one of the histological hallmarks of Alzheimer's disease. Aβ can also aggregate at a peripheral synapse, the neuromuscular junction, in the form of intracellular lesions characteristic of the degenerative muscle disease termed sporadic inclusion body myositis. The relationship between the increased production and aggregation of Aβ and the synaptic dysfunction observed in the two disorders is not clear, but the similarities point to the important role of APP in cholinergic synapses. Here we review the biological functions of APP under normal conditions and their dysfunctional counterparts in an attempt to explain the involvement of this protein in cholinergic synaptopathies in general.