Your browser doesn't support javascript.
loading
Ca2+ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer's Disease.
McDaid, John; Mustaly-Kalimi, Sarah; Stutzmann, Grace E.
Afiliação
  • McDaid J; Center for Neurodegenerative Disease and Therapeutics, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Rd., North Chicago, IL 60064, USA.
  • Mustaly-Kalimi S; School of Graduate and Postdoctoral Studies, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Rd., North Chicago, IL 60064, USA.
  • Stutzmann GE; Center for Neurodegenerative Disease and Therapeutics, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Rd., North Chicago, IL 60064, USA.
Cells ; 9(12)2020 12 10.
Article em En | MEDLINE | ID: mdl-33321866
Ca2+ homeostasis is essential for multiple neuronal functions and thus, Ca2+ dyshomeostasis can lead to widespread impairment of cellular and synaptic signaling, subsequently contributing to dementia and Alzheimer's disease (AD). While numerous studies implicate Ca2+ mishandling in AD, the cellular basis for loss of cognitive function remains under investigation. The process of synaptic degradation and degeneration in AD is slow, and constitutes a series of maladaptive processes each contributing to a further destabilization of the Ca2+ homeostatic machinery. Ca2+ homeostasis involves precise maintenance of cytosolic Ca2+ levels, despite extracellular influx via multiple synaptic Ca2+ channels, and intracellular release via organelles such as the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) and IP3R, lysosomes via transient receptor potential mucolipin channel (TRPML) and two pore channel (TPC), and mitochondria via the permeability transition pore (PTP). Furthermore, functioning of these organelles relies upon regulated inter-organelle Ca2+ handling, with aberrant signaling resulting in synaptic dysfunction, protein mishandling, oxidative stress and defective bioenergetics, among other consequences consistent with AD. With few effective treatments currently available to mitigate AD, the past few years have seen a significant increase in the study of synaptic and cellular mechanisms as drivers of AD, including Ca2+ dyshomeostasis. Here, we detail some key findings and discuss implications for future AD treatments.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sinapses / Sinalização do Cálcio / Doença de Alzheimer Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sinapses / Sinalização do Cálcio / Doença de Alzheimer Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article