| Organelle stress sensors and cell death mechanisms in neurodegenerative diseases. | |
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MedLine Citation:
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PMID: 20942793 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Neurodegenerative diseases trigger neuronal cell death by a variety of endogenous suicide pathways. Although cell death may occur through highly heterogeneous processes, specific cell organelles and stress sensors have shown promise as potential therapeutic targets. The plasma membrane senses stress through residing receptors, which can directly or indirectly activate apoptosis. Importantly, several events involved in neuronal death also affect mitochondria homeostasis, leading to calcium uptake, opening of the permeability transition pore, and release of apoptogenic factors. In addition, nuclear DNA damage triggers cell death, where p53 is activated to modulate the expression of selected apoptosis target genes. Signaling proteins implicated in apoptosis pathways are enriched at the Golgi complex, including death receptors and the phosphoinositide 3-kinase. Finally, neurodegenerative diseases progress with accumulation of misfolded proteins, deficiently removed by intracellular proteases or chaperones, and transport abnormalities due to disturbance of cytoskeletal organization in degenerating neurons. The challenge is to decode the complex signaling network of inter-organellar crosstalk leading to cell death and identify therapeutic approaches for delaying or preventing neurodegenerative diseases. |
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Authors:
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Ricardo J S Viana; Maria B Fonseca; Rita M Ramalho; Ana F Nunes; Cecília M P Rodrigues |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: CNS & neurological disorders drug targets Volume: 9 ISSN: 1996-3181 ISO Abbreviation: CNS Neurol Disord Drug Targets Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101269155 Medline TA: CNS Neurol Disord Drug Targets Country: United Arab Emirates |
Other Details:
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Languages: eng Pagination: 679-92 Citation Subset: IM |
Affiliation:
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Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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