title: Disruption of transforming growth factor-β superfamily signaling: A shared mechanism underlying hereditary cerebral small vessel disease.
abstract: Cerebral small vessel disease (SVD) is not only one of the leading causes of cognitive impairment but also an important contributory factor in Alzheimer's disease. SVD and related white matter changes are common in the elderly, but the underlying pathogenic mechanism remains unclear. The end-stage pathology of SVD often involves replacement of vascular smooth muscle cells with collagenous or other nontensile fibrillary material. Recent studies on hereditary SVD have revealed a close relationship between small vessel pathology and disruption of transforming growth factor-β (TGF-β) superfamily signaling. TGF-β superfamily members, such as TGF-β and bone morphogenetic proteins, are multifunctional proteins that regulate production of extracellular matrix proteins, which in turn control the bioavailability of TGF-β superfamily members and modulate their signaling activities. This article reviews hereditary disorders with small vessel pathology and their relation to TGF-β superfamily signaling.
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Neurology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan. Electronic address: ihara@ncvc.go.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
mesh_terms: D000818:Animals; D059345:Cerebral Small Vessel Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta
keywords: BMP; Extracellular matrix; Hereditary small vessel disease; Pathogenesis; TGF-β