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Dysfunction of TGF-β1 signaling in Alzheimer's disease: perspectives for neuroprotection.
MedLine Citation:
PMID:  21879289     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Alzheimer's disease (AD) is a neurodegenerative disorder that affects about 35 million people worldwide. Current drugs for AD only treat the symptoms and do not interfere with the underlying pathogenic mechanisms of the disease. AD is characterized by the presence of β-amyloid (Aβ) plaques, neurofibrillary tangles, and neuronal loss. Identification of the molecular determinants underlying Aβ-induced neurodegeneration is an essential step for the development of disease-modifying drugs. Recently, an impairment of the transforming growth factor-β1 (TGF-β1) signaling pathway has been demonstrated to be specific to the AD brain and, particularly, to the early phase of the disease. TGF-β1 is a neurotrophic factor responsible for the initiation and maintenance of neuronal differentiation and synaptic plasticity. The deficiency of TGF-β1 signaling is associated with Aβ pathology and neurofibrillary tangle formation in AD animal models. Reduced TGF-β1 signaling seems to contribute both to microglial activation and to ectopic cell-cycle re-activation in neurons, two events that contribute to neurodegeneration in the AD brain. The neuroprotective features of TGF-β1 indicate the advantage of rescuing TGF-β1 signaling as a means to slow down the neurodegenerative process in AD.
Authors:
Filippo Caraci; Simona Spampinato; Maria Angela Sortino; Paolo Bosco; Giuseppe Battaglia; Valeria Bruno; Filippo Drago; Ferdinando Nicoletti; Agata Copani
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-31
Journal Detail:
Title:  Cell and tissue research     Volume:  -     ISSN:  1432-0878     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417625     Medline TA:  Cell Tissue Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Drug Sciences, University of Catania, Viale Andrea Doria 6, 95125, Catania, Italy, fcaraci@unict.it.
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