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Cited by 77Neurological Disease Mechanisms and TreatmentsBarrier Structure and Function StudiesNeuroinflammation and Neurodegeneration Mechanisms

TGF-β Signaling: A Therapeutic Target to Reinstate Regenerative Plasticity in Vascular Dementia?

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Kandasamy, Mahesh, Anusuyadevi, Muthuswamy, Aigner, Kiera M, Unger, Michael S, Kniewallner, Kathrin M, Sousa, Diana M Bessa de, Altendorfer, Barbara, Mrowetz, Heike +2 more·2020·Aging and disease
DOI 10.14336/ad.2020.0222PMC PMC7390515
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Abstract

Vascular dementia (VaD) is the second leading form of memory loss after Alzheimer's disease (AD). Currently, there is no cure available. The etiology, pathophysiology and clinical manifestations of VaD are extremely heterogeneous, but the impaired cerebral blood flow (CBF) represents a common denominator of VaD. The latter might be the result of atherosclerosis, amyloid angiopathy, microbleeding and micro-strokes, together causing blood-brain barrier (BBB) dysfunction and vessel leakage, collectively originating from the consequence of hypertension, one of the main risk factors for VaD. At the histopathological level, VaD displays abnormal vascular remodeling, endothelial cell death, string vessel formation, pericyte responses, fibrosis, astrogliosis, sclerosis, microglia activation, neuroinflammation, demyelination, white matter lesions, deprivation of synapses and neuronal loss. The transforming growth factor (TGF) β has been identified as one of the key molecular factors involved in the aforementioned various pathological aspects. Thus, targeting TGF-β signaling in the brain might be a promising therapeutic strategy to mitigate vascular pathology and improve cognitive functions in patients with VaD. This review revisits the recent understanding of the role of TGF-β in VaD and associated pathological hallmarks. It further explores the potential to modulate certain aspects of VaD pathology by targeting TGF-β signaling.

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  • TGFβ1 is implicated in vascular dementia to promote abnormal vascular remodeling and was proposed as a therapeutic target for AD.

    “Moreover, TGFβ1 is implicated in vascular dementia to promote abnormal vascular remodeling and was proposed as a therapeutic target for AD 59 .”

    From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [59]

    The sections on VaD pathogenesis and vascular remodeling link TGF-β1 to vascular degeneration, fibrosis, and abnormal remodeling in vascular dementia. The paper proposes targeting TGF-β signaling to treat vascular dementia, but does not specifically propose it as a therapeutic target for Alzheimer’s disease (pages unavailable in our copy). (LLM, conf=0.87)

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Authors
Kandasamy, M., Anusuyadevi, M., Aigner, K. M., Unger, M. S., Kniewallner, K. M., Sousa, D. M. B. D., Altendorfer, B., Mrowetz, H., Bogdahn, U., & Aigner, L.
Affiliations
  • University Grants Commission (IN)
  • Bharathidasan University (IN)
  • Paracelsus Medical University (AT)
Corresponding author
Aigner, Ludwig
ORCID
Venue
Aging and disease
Publisher
Aging and Disease
Published
2020
Volume
11
Issue
4
Pages
828
ISSN
2152-5250 (ISSN-L)
DOI
10.14336/ad.2020.0222
PMC
PMC7390515
OpenAlex
W3046693269
Cited by
77
References
26
Citations by year
2026: 3 · 2025: 17 · 2024: 12 · 2023: 20 · 2022: 12 · 2021: 11 · 2020: 2
FWCI
1.12
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • European Commission (2007–2013, FP7 2007-2013, FP7/2007, 278850)
  • Department of Science and Technology, Ministry of Science and Technology, India
  • University Grants Commission (/2007)
  • Austrian Science Fund (P31362, F4413-B23, F4413)
  • Science and Engineering Research Board (SERB EEQ/2016/000639, SERB-ECR/2016/000741)
Topics
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
vascular dementia, TGF-beta signaling, therapeutic target, cerebral blood flow, blood-brain barrier dysfunction, hypertension, neuroinflammation, vascular remodeling, pericytes, astrocyte activation, cognitive impairment, TGF-beta inhibition

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