Neuronal Calcium Mishandling and the Pathogenesis of Alzheimer’s Disease
By Ilya Bezprozvanny, Mark P. Mattson. Trends in Neurosciences, 2008
921 citations recorded by the source corpus.
Perturbed neuronal Ca2+ homeostasis is implicated in age-related cognitive impairment and Alzheimer’s disease (AD). With advancing age neurons encounter increased oxidative stress and impaired energy metabolism, which compromise the function of proteins that control membrane excitability and subcellular Ca2+ dynamics. Toxic forms of amyloid β-peptide (Aβ) may induce Ca2+ influx into neurons by inducing membrane-associated oxidative stress or by forming an oligomeric pore in the membrane, thereby rendering neurons vulnerable to excitotoxicity and apoptosis. AD-causing mutations in the β-amyloid precursor protein and presenilins may compromise normal of these proteins in the plasma membrane and endoplasmic reticulum, respectively. Emerging knowledge of the actions of Ca2+ upstream and downstream of Aβ provide opportunities to develop novel preventative and therapeutic interventions for AD.
Subfields: Cell Biology, Pharmacology, Physiology
View Paper: https://www.semanticscholar.org/paper/046d02e25e262132d7a19317c1420f267ed806dc
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Citations in the corpus
- Recent advances in Alzheimer’s disease: mechanisms, clinical trials and new drug development strategies (2024, background): “290 A β may increase cytosolic calcium levels and impair mitochondrial calcium buffering functions through various pathways including plasma membrane receptors and calcium channels, 291 enhanced ER calcium release, 292 and the mitochondrial inner membrane calcium channel MCU.”
- Upregulated function of mitochondria-associated ER membranes in Alzheimer disease (2012, positive): “…cholesterol (Stefani and Liguri, 2009), altered phospholipid metabolism (Wells et al , 1995; Pettegrew et al , 2001), aberrant calcium homeostasis (Bezprozvanny and Mattson, 2008), and mitochondrial dysfunction (Wang et al , 2009)— detected in tissues and in cultured cells from AD patients…”
- Basis for a neuronal version of Grover's quantum algorithm (2014, background): “…cleft widths, intracellular molecular and vesicular trafficking, membrane repair, synaptogenesis, neurite growth, and efficacious synaptic transmission (e.g., Malenka and Bear, 2004; Verkhratsky, 2005; Bezprozvanny and Mattson, 2008; Craddock et al., 2010; Priel et al., 2010; Dent et al., 2011).”
- Calcium and ROS: A mutual interplay (2015, background): “Oxidative modification and subsequent degradation of the PMCA protein has been found in models of global ischemia-reperfusion injury and seizures [15].”
- Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease (2017, background): “homeostasis, and altered regulation of transcription of genes important for neuronal development and plasticity [47, 163].”
- Mitophagy and Alzheimer’s disease: cellular and molecular mechanisms (2017, background): “Furthermore, mitochondria regulate Ca2+, and perturbed neuronal Ca2+ levels lead to neuronal death and are implicated in neurodegenerative diseases, including AD [14].”
- Critical role of soluble amyloid-β for early hippocampal hyperactivity in a mouse model of Alzheimer’s disease (2012, background): “Asmentioned above, the neuronal Ca homeostasis may be altered in transgenic mice (6, 21, 22).”