期刊
IUBMB LIFE
卷 60, 期 9, 页码 575-590出版社
WILEY
DOI: 10.1002/iub.91
关键词
Ca2+ signaling; Ca2+ homeostasis; Alzheimer's disease; Parkinson's disease; Huntington's disease; autosomal dominant spinocerebellar ataxias; glaucoma; amyotrophic lateral sclerosis; epilepsy; schizophrnia; traumatic brain injury; brain stroke; HIV dementia
资金
- EU consortium PROMEMORIA [LSHM-CT-2005-512012]
- Polish ordered research [PBZ-KBN-124/P05/2004]
- Foundation for Polish Science
Neuronal Ca2+ homeostasis and Ca2+, signaling regulate multiple neuronal functions, including synaptic transmission, plasticity, and cell survival. Therefore disturbances in Ca2+ homeostasis can affect the well-being or the neuron in different ways and to various degrees. Ca2+ homeostasis undergoes subtle dysregulation in the physiological ageing. Products of energy metabolism accumulating with age together with oxidative stress gradually impair Ca2+ homeostasis, making neurons more vulnerable to additional stress which, in turn, can lead to neuronal degeneration. Neurodegenerative diseases related to aging, such as Alzheimer's disease., Parkinson's disease, or Huntington's disease, develop slowly and are characterized by the positive feedback between Ca2+ dyshomeostasis and the aggregation of disease-related proteins such as amyloid beta, alfa-synuclein, or huntingtin. Ca2+ dyshomeostasis escalates with time eventually leading to neuronal loss. Ca2+ dyshomeostasis in these chronic pathologies comprises mitochondrial and endoplasmic reticulum dysfunction, Ca2+ buffering impairment, glutamate excitotoxicity and alterations in Ca2+ entry routes into neurons. Similar changes have been described in a group of multifactorial diseases not related to ageing, such as epilepsy, schizophrenia, amyotrophic lateral sclerosis, or glaucoma. Dysregulation of Ca2+ homeostasis caused by HIV infection or by sudden accidents, such as brain stroke or traumatic brain injury, leads to rapid neuronal death. The differences between the distinct types of Ca2+ dyshomeostasis underlying neuronal degeneration in various types of pathologies are not clear. Questions that should be addressed concern the sequence of pathogenic events in an affected neuron and the pattern of progressive degeneration in the brain itself. Moreover, elucidation of the selective vulnerability of various types of neurons affected in the diseases described here will require identification of differences in the types of Ca2+ homeostasis and signaling among these neurons. This information will be required for improved targeting of Ca2+ homeostasis and signaling components in future therapeutic strategies, since no effective treatment is currently available to prevent neuronal degeneration in any of the pathologies described here. (C) 2008 IUBMB.
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