title: Dysfunction of TGF-β1 signaling in Alzheimer's disease: perspectives for neuroprotection.
abstract: 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: Department of Drug Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy. fcaraci@unict.it
authors: Filippo
authors: F
authors: Caraci
authors: Simona
authors: S
authors: Spampinato
authors: Maria Angela
authors: MA
authors: Sortino
authors: Paolo
authors: P
authors: Bosco
authors: Giuseppe
authors: G
authors: Battaglia
authors: Valeria
authors: V
authors: Bruno
authors: Filippo
authors: F
authors: Drago
authors: Ferdinando
authors: F
authors: Nicoletti
authors: Agata
authors: A
authors: Copani
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D006801:Humans; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1