TGF-β1 pathway as a new target for neuroprotection in Alzheimer's disease.
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.
Caraci
Filippo
F
Department of Pharmaceutical Sciences, University of Catania, Italy. carafil@hotmail.com
Battaglia
Giuseppe
G
Bruno
Valeria
V
Bosco
Paolo
P
Carbonaro
Viviana
V
Giuffrida
Maria Laura
ML
Drago
Filippo
F
Sortino
Maria Angela
MA
Nicoletti
Ferdinando
F
Copani
Agata
A
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*
D018696:Neuroprotective Agents; D053773:Transforming Growth Factor beta1