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Transforming-Growth-Factor-尾1 (TGF-尾1) is an anti-inflammatory cytokine that exerts neuroprotective effects against
锟�-amyloid (A尾)-induced neurodegeneration. An impairment of TGF-尾1 signaling pathway has been demonstrated in
an early phase of Alzheimer锟絪 disease (AD) pathogenesis. Deficit of TGF-尾1 seems to be a common pathophysiological event
both in depression and AD. Depressive symptoms may be among the earliest symptoms of preclinical stages of AD and a
long-term treatment with antidepressants is known to reduce the risk to develop AD. Plasma TGF-锟�1 levels are reduced
in depressed patients, and, interestingly, different second-generation antidepressants increase circulating TGF-锟�1 levels in
depressed patients. Whereas these data identify TGF-尾1 signaling as a potential common target for both depression and
AD, the potential neuroprotective activity of antidepressants against A尾-induced neurodegeneration in vitro has been only
partially explored. We examined the neuroprotective activity of fluoxetine and sertraline both in pure and mixed rat neuronal
cultures challenged with synthetic Ab(1-42) oligomers (100 nM) for 48 hours. We found that therapeutic concentrations
(100 nM-1 渭M) of fluoxetine and sertraline significantly prevented A尾-induced toxicity in mixed cultures, but not in pure
neuronal cultures. A neutralizing antibody against TGF-锟�1 (2 渭g/ml) prevented the neuroprotective effects of antidepressant
drugs against A尾-induced neurodegeneration in mixed cultures. Consistent with a glia-mediated effect, a 24 hr treatment of
astrocytes with fluoxetine promoted the release of active TGF-尾1 in the culture media. Our data demonstrate that secondgeneration
antidepressants are neuroprotective in vitro against A锟�-induced neurodegeneration by rescuing TGF-尾1 signaling
and suggest that these drugs might represent new neuroprotective tools for the treatment of AD.
Biography
Filippo Caraci is Assistant Professor of Psychopharmacology at the Department of Educational Sciences of the University of Catania. He has worked in the field of
Neuropharmacology focusing his attention on the neurobiology of Alzheimer锟絪 disease with the aim to identify new pharmacological targets. He has published more
than 60 papers in peer reviewed journals and serving as referee for several international journals in the fields of pharmacology. He is an associate faculty member
of F1000 and he is also Reviewing Editor of Frontiers in Experimental Pharmacology and Drug Discovery.
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