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Dysfunction of TGF-β1 signaling in Alzheimer’s disease: perspectives for neuroprotection

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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.

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Authors and Affiliations

  1. Department of Drug Sciences, University of Catania, Viale Andrea Doria 6, 95125, Catania, Italy

    Filippo Caraci & Agata Copani

  2. Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, 95125, Catania, Italy

    Simona Spampinato, Maria Angela Sortino & Filippo Drago

  3. IRCCS Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, 94018, Troina, Italy

    Paolo Bosco

  4. I.N.M. Neuromed, Località Camerelle, 86077, Pozzilli, Italy

    Giuseppe Battaglia, Valeria Bruno & Ferdinando Nicoletti

  5. Department of Human Physiology and Pharmacology, University of Rome Sapienza, 00185, Rome, Italy

    Ferdinando Nicoletti

  6. I.B.B., CNR-Catania, 95125, Catania, Italy

    Agata Copani

  7. PhD Program in Neuropharmacology, University of Catania, Catania, Italy

    Simona Spampinato

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  1. Filippo Caraci
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  2. Simona Spampinato
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  9. Agata Copani
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Correspondence to Filippo Caraci.

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Ferdinando Nicoletti and Agata Copani are co-senior authors.

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Caraci, F., Spampinato, S., Sortino, M.A. et al. Dysfunction of TGF-β1 signaling in Alzheimer’s disease: perspectives for neuroprotection. Cell Tissue Res 347, 291–301 (2012). https://doi.org/10.1007/s00441-011-1230-6

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