Neurobiological links between depression and AD: the role of TGF-β1 signaling as a new pharmacological target

Caraci, F; Spampinato, Sf; Morgese, Mg; Tascedda, F; Salluzzo, Mg; Giambirtone, Mc; Caruso, G; Munafò, A; Torrisi, Sa; Leggio, Gm; Trabace, L; Nicoletti, F; Drago, F; Sortino, Ma; Copani, A

doi:10.1016/j.phrs.2018.02.007

In the last several years a large number of studies have demonstrated the neurobiological and clinical continuum between depression and Alzheimer’s disease (AD). Depression is a risk factor for the development of AD, and the presence of depressive symptoms significantly increases the conversion of Mild Cognitive Impairment (MCI) into AD.Commonpathophysiological events have been identified in depression and AD, including neuroinflammationwith an aberrant Tumor Necrosis Factor-α(TNF-α)signaling,and an impairment ofBrain-Derived Neurotrophic Factor(BDNF) and Transforming-Growth-Factor-β1 (TGF-β1) signalingTGF-β1is an anti-inflammatory cytokine that exerts neuroprotective effects againstamyloid-β (Aβ)-induced neurodegeneration,andit has a key role in memory formation and synaptic plasticity. TGF-β1 plasmalevels are reduced in major depressed patients (MDD), correlate with depression severity and significantly contribute to treatment resistance in MDD. The deficit of Smad-dependent TGF-β1 signaling is also an early event in AD pathogenesis, whichcontributes to inflammaging and cognitive decline in AD. A long-term treatment with antidepressants such as selective-serotonin-reuptake inhibitors (SSRIs) is known to reduce the risk of AD in patients with depression and, SSRIs, such as fluoxetine, increase the release of TGF-β1 from astrocytes and exert relevant neuroprotective effects in experimental models of AD..

Titolo:	Neurobiological links between depression and AD: the role of TGF-β1 signaling as a new pharmacological target
Autori interni:	CARACI, FILIPPO (Primo) [Conceptualization] (Corresponding) SPAMPINATO, SIMONA FEDERICA Morgese MG Tascedda F Salluzzo MG Giambirtone MC CARUSO, GIUSEPPE [Writing – Review & Editing] Munafò A TORRISI, SEBASTIANO ALFIO [Writing – Review & Editing] LEGGIO, GIAN MARCO [Writing – Review & Editing] Trabace L Nicoletti F DRAGO, Filippo SORTINO, Maria Angela [Conceptualization] COPANI, Agata Graziella [Writing – Original Draft Preparation] mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2018
Rivista:	PHARMACOLOGICAL RESEARCH
Handle:	http://hdl.handle.net/20.500.11769/316422
Appare nelle tipologie:	1.1 Articolo in rivista

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http://hdl.handle.net/20.500.11769/316422

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