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Cited by 38Neuroscience and Neuropharmacology ResearchTGF-β signaling in diseasesNeurogenesis and neuroplasticity mechanisms

Activin Signaling in the Pathogenesis and Therapy of Neuropsychiatric Diseases

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Link, Andrea S., Zheng, Fang, Alzheimer, Christian·2016·Frontiers in Molecular Neuroscience
DOI 10.3389/fnmol.2016.00032PMC PMC4861723
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Abstract

Activins are members of the transforming growth factor β (TGFβ) family and serve as multifunctional regulatory proteins in many tissues and organs. In the brain, activin A, which is formed by two disulfide-linked βA subunits, is recognized as the predominant player in activin signaling. Over the last years, considerable progress has been made in elucidating novel and unexpected functions of activin in the normal and diseased brain and in deciphering the underlying molecular mechanisms. Initially identified as a neurotrophic and protective factor during development and in several forms of acute injury, the scope of effects of activin A in the adult central nervous system (CNS) has been considerably broadened by now. Here, we will highlight recent findings that bear significance for a better understanding of the pathogenesis of various neuropsychiatric diseases and might hold promise for novel therapeutic strategies. While the basal level of activin A in the adult brain is low, significant short-term up-regulation occurs in response to increased neuronal activity. In fact, brief exposure to an enriched environment (EE) is already sufficient to considerably strengthen activin signaling. Enhancement of this pathway tunes the performance of glutamatergic and GABAergic synapses in a fashion that impacts on cognitive functions and affective behavior, counteracts death-inducing signals through extrasynaptic NMDA receptors (NMDARs), and stimulates adult neurogenesis in the hippocampus. We will discuss how impaired activin signaling is involved in anxiety disorders, depression, drug dependence, and neurodegenerative diseases such as Alzheimer's and Parkinson's, and how reinforcement of activin signaling might be exploited for therapeutic interventions.

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  • Activin regulates brain circuits under normal physiological conditions and is neuroprotective against acute and chronic brain damage.

    “Interestingly, activin, a regulatory protein in the TGFβ family, not only regulates brain circuits under normal physiological conditions, but is also neuroprotective against acute and chronic brain damage [95].”

    From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [95]

  • Impaired activin signaling is associated with Parkinson's disease, Alzheimer's disease, anxiety disorders, depression, and drug dependence.

    “Impaired activin signaling has been associated with Parkinson’s disease and Alzheimer’s disease as well as anxiety disorders, depression, and drug dependence [95].”

    From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [95]

  • Activin promotes neuroprotection by regulating balance of synaptic and extrasynaptic NMDA receptors.

    “Recent evidence indicates that activin promotes neuroprotection by regulating the balance of synaptic and extrasynaptic NMDA receptors [95,96].”

    From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [95]

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Cited by

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Authors
Link, A. S., Zheng, F., & Alzheimer, C.
Affiliations
Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
Corresponding author
Alzheimer, Christian
ORCID
Alzheimer, Christian
Venue
Frontiers in Molecular Neuroscience
Publisher
Frontiers Media SA
Published
2016-05-10
Volume
9
Pages
32-32
ISSN
1662-5099 (ISSN-L)
DOI
10.3389/fnmol.2016.00032
PMC
PMC4861723
OpenAlex
W2353648028
Cited by
38
References
4
Citations by year
2026: 4 · 2025: 2 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 4
FWCI
0.30
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • OPUS Repository (Kooperativer Bibliotheksverbund Berlin-Brandenburg) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Jürgen Manchot Stiftung
  • Johannes und Frieda Marohn-Stiftung
  • Deutsche Forschungsgemeinschaft (INST 90/675-1, INST 90/675-1 FUGG)
  • Eidgenössische Technische Hochschule Zürich
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
activin A, activin signaling, TGF-beta superfamily, neuropsychiatric disorders, environmental enrichment, neuronal activity, glutamatergic synapses, GABAergic synapses, extrasynaptic NMDA receptors, adult neurogenesis, hippocampus, anxiety disorders, depression, drug addiction, Alzheimer's disease, Parkinson's disease, neurodegeneration, cognitive function, emotional behavior

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