期刊
NEUROBIOLOGY OF DISEASE
卷 46, 期 3, 页码 508-526出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2011.10.019
关键词
Parkinson disease; Amygdala; Olfaction; Autonomic nervous system; Sleep disorders; Dementia; Psychiatric symptoms; Transcriptomics; Proteomics; Oxidative stresss; Ubiquitin-proteasome system; Redox proteomics; Lipids; Mitochondria
资金
- Spanish Ministry of Health
- Institut de Salud Carlos III [PI05/1570, PI05/2214, PI08/0582, FIS PI11/0968]
- European Commission [LSHM-CT-2004-503039]
- INDABIP [FP6-2005-LIFESCIHEALTH-7]
- ICREA Funding Source: Custom
Parkinson disease (PD) is a systemic disease with variegated non-motor deficits and neurological symptoms, including impaired olfaction, autonomic failure, cognitive impairment and psychiatric symptoms, in addition to the classical motor symptoms. Many non-motor symptoms appear before or in parallel with motor deficits and then worsen with disease progression. Although there is a relationship, albeit not causal, between motor symptoms and the presence of Lewy bodies (LBs) and neurites filled with abnormal alpha-synuclein, other neurological alterations are independent of the amount of alpha-synuclein inclusions in neurons and neurites, thereby indicating that different mechanisms probably converge in the degenerative process. This may apply to complex alterations interfering with olfactory and autonomic nervous system functions, emotions, sleep regulation, and behavioral, cognitive and mental performance. Involvement of the cerebral cortex leading to impaired behavior and cognition is related to several convergent altered factors including: a. dopaminergic, noradrenergic, serotoninergic and cholinergic cortical innervation; b. synapses; c. cortical metabolism; d. mitochondrial function and energy production; e. oxidative damage; f. transcription; g. protein expression; h. lipid composition; and i. ubiquitin-proteasome system and autophagy, among others. This complex situation indicates that multiple subcellular failure in selected cell populations is difficult to reconcile with a reductionistic scenario of a single causative cascade of events leading to non-motor symptoms in PD. Furthermore, these alterations may appear at early stages of the disease and may precede the appearance of substantial irreversible cell loss by years. These observations have important implications in the design of therapeutic approaches geared to prevention and treatment of PD. (C) 2011 Elsevier Inc. All rights reserved.
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