PMID- 33669577
OWN - NLM
STAT- MEDLINE
DCOM- 20210416
LR  - 20210416
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 4
DP  - 2021 Feb 19
TI  - Homocysteine in Neurology: A Possible Contributing Factor to Small Vessel 
      Disease.
LID - 10.3390/ijms22042051 [doi]
LID - 2051
AB  - Homocysteine (Hcy) is a sulfur-containing amino acid generated during methionine 
      metabolism, accumulation of which may be caused by genetic defects or the deficit 
      of vitamin B12 and folate. A serum level greater than 15 micro-mols/L is defined 
      as hyperhomocysteinemia (HHcy). Hcy has many roles, the most important being the 
      active participation in the transmethylation reactions, fundamental for the 
      brain. Many studies focused on the role of homocysteine accumulation in vascular 
      or degenerative neurological diseases, but the results are still undefined. More 
      is known in cardiovascular disease. HHcy is a determinant for the development and 
      progression of inflammation, atherosclerotic plaque formation, endothelium, 
      arteriolar damage, smooth muscle cell proliferation, and altered-oxidative stress 
      response. Conversely, few studies focused on the relationship between HHcy and 
      small vessel disease (SVD), despite the evidence that mice with HHcy showed a 
      significant end-feet disruption of astrocytes with a diffuse SVD. A severe 
      reduction of vascular aquaporin-4-water channels, lower levels of 
      high-functioning potassium channels, and higher metalloproteinases are also 
      observed. HHcy modulates the N-homocysteinylation process, promoting a 
      pro-coagulative state and damage of the cellular protein integrity. This altered 
      process could be directly involved in the altered endothelium activation, typical 
      of SVD and protein quality, inhibiting the ubiquitin-proteasome system control. 
      HHcy also promotes a constant enhancement of microglia activation, inducing the 
      sustained pro-inflammatory status observed in SVD. This review article addresses 
      the possible role of HHcy in small-vessel disease and understands its pathogenic 
      impact.
FAU - Moretti, Rita
AU  - Moretti R
AUID- ORCID: 0000-0002-9731-2697
AD  - Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 
      Trieste, Italy.
FAU - Giuffre, Mauro
AU  - Giuffre M
AUID- ORCID: 0000-0002-9910-3514
AD  - Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 
      Trieste, Italy.
FAU - Caruso, Paola
AU  - Caruso P
AD  - Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 
      Trieste, Italy.
FAU - Gazzin, Silvia
AU  - Gazzin S
AUID- ORCID: 0000-0001-9403-3564
AD  - Italian Liver Foundation, AREA SCIENCE PARK, 34149 Trieste, Italy.
FAU - Tiribelli, Claudio
AU  - Tiribelli C
AUID- ORCID: 0000-0001-6596-7595
AD  - Italian Liver Foundation, AREA SCIENCE PARK, 34149 Trieste, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210219
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Animals
MH  - Brain/*blood supply/*pathology
MH  - Cerebrovascular Disorders/*metabolism
MH  - Homocysteine/*metabolism
MH  - Humans
MH  - Inflammation/pathology
MH  - Nerve Degeneration
MH  - Oxidative Stress
PMC - PMC7922986
OTO - NOTNLM
OT  - SVD
OT  - homocysteine
OT  - neurodegeneration
OT  - neuroinflammation
OT  - oxidative stress
COIS- The authors declare no conflict of interest.
EDAT- 2021/03/07 06:00
MHDA- 2021/04/17 06:00
PMCR- 2021/02/19
CRDT- 2021/03/06 01:05
PHST- 2021/01/31 00:00 [received]
PHST- 2021/02/14 00:00 [revised]
PHST- 2021/02/15 00:00 [accepted]
PHST- 2021/03/06 01:05 [entrez]
PHST- 2021/03/07 06:00 [pubmed]
PHST- 2021/04/17 06:00 [medline]
PHST- 2021/02/19 00:00 [pmc-release]
AID - ijms22042051 [pii]
AID - ijms-22-02051 [pii]
AID - 10.3390/ijms22042051 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Feb 19;22(4):2051. doi: 10.3390/ijms22042051.