title: TGF-β1 pathway as a new target for neuroprotection in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder that affects more than 37 million people worldwide. Current drugs for AD are only symptomatic, but do not interfere with the underlying pathogenic mechanisms of the disease. AD is characterized by the presence of ß-amyloid (Aβ) plaques, neurofibrillary tangles, and neuronal loss. The identification of the molecular determinants underlying AD pathogenesis is a fundamental step to design new disease-modifying drugs. Recently, a specific impairment of transforming-growth-factor-β1 (TGF-β1) signaling pathway has been demonstrated in AD brain. The deficiency of TGF-β1 signaling has been shown to increase both Aβ accumulation and Aβ-induced neurodegeneration in AD models. The loss of function of TGF-ß1 pathway seems also to contribute to tau pathology and neurofibrillary tangle formation. Growing evidence suggests a neuroprotective role for TGF-β1 against Aβ toxicity both in vitro and in vivo models of AD. Different drugs, such as lithium or group II mGlu receptor agonists are able to increase TGF-β1 levels in the central nervous system (CNS), and might be considered as new neuroprotective tools against Aβ-induced neurodegeneration. In the present review, we examine the evidence for a neuroprotective role of TGF-β1 in AD, and discuss the TGF-β1 signaling pathway as a new pharmacological target for the treatment of AD.
authors.affiliation: Department of Pharmaceutical Sciences, University of Catania, Italy. carafil@hotmail.com
authors.forename: Filippo
authors.initials: F
authors.lastname: Caraci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia
authors.forename: Valeria
authors.initials: V
authors.lastname: Bruno
authors.forename: Paolo
authors.initials: P
authors.lastname: Bosco
authors.forename: Viviana
authors.initials: V
authors.lastname: Carbonaro
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Giuffrida
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Sortino
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Agata
authors.initials: A
authors.lastname: Copani
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D015398:Signal Transduction / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D053773:Transforming Growth Factor beta1