Pathomechanism of leukoaraiosis: A molecular bridge between the genetic, biochemical, and clinical processes (a mitochondrial hypothesis)

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Ischemic demyelination in the white matter of the brain is a frequent clinical entity. In neuroimaging terms, it is referred to as leukoaraiosis (LA). LA can reflect a broad public health problem, which is caused by a cognitive impairment ranging from mild slowness of thinking to full-blown subcortical dementia. One-quarter of subjects aged 65 yr or over are affected by some degree of white matter changes. There are a number of genetic factors that can be associated with circulatory disturbances of the white matter of the brain. A slight chronic hypoperfusion or an endothelial dysfunction associated with unfavorable genetic variations such as methylenetetrahydrofolate reductase C677T variation and angiotensin-converting enzyme I/D polymorphism then may lead indirectly to a malfunction of the molecular cross-talk between the nucleus and the mitochondria. This results in a decrease in the production of energy in the glia cells and thereby the beginning of demyelination. From another aspect, the presence of either the apolipoprotein E 2 or 4 alleles may cause an increased vulnerability to a slight chronic hypoperfusion of the white matter by reducing the range of mechanical and chemical flexibility of the glial cytoskeleton. In consequence of the chronic hypoperfusion, the functionally damaged kinesin protein gives rise also to the disturbances of the trafficking of the myelin basic protein mRNAs in the oligodendrocytes. On the basis of the current knowledge on LA, this article suggests a hypothetical molecular bridge between the genetic, biochemical, and clinical processes.

Original languageEnglish
Pages (from-to)21-34
Number of pages14
JournalNeuroMolecular Medicine
Volume9
Issue number1
DOIs
Publication statusPublished - Feb 2007

Fingerprint

Biochemical Phenomena
Leukoaraiosis
Demyelinating Diseases
Neuroglia
Apolipoprotein E2
Apolipoprotein E4
Methylenetetrahydrofolate Reductase (NADPH2)
Kinesin
Myelin Basic Protein
Oligodendroglia
Brain
Peptidyl-Dipeptidase A
Cytoskeleton
Neuroimaging
Dementia
Mitochondria
Public Health
Alleles
Messenger RNA
White Matter

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics
  • Cell Biology

Cite this

@article{13aad6a6a8f44f5faeacd4f159fe0c9e,
title = "Pathomechanism of leukoaraiosis: A molecular bridge between the genetic, biochemical, and clinical processes (a mitochondrial hypothesis)",
abstract = "Ischemic demyelination in the white matter of the brain is a frequent clinical entity. In neuroimaging terms, it is referred to as leukoaraiosis (LA). LA can reflect a broad public health problem, which is caused by a cognitive impairment ranging from mild slowness of thinking to full-blown subcortical dementia. One-quarter of subjects aged 65 yr or over are affected by some degree of white matter changes. There are a number of genetic factors that can be associated with circulatory disturbances of the white matter of the brain. A slight chronic hypoperfusion or an endothelial dysfunction associated with unfavorable genetic variations such as methylenetetrahydrofolate reductase C677T variation and angiotensin-converting enzyme I/D polymorphism then may lead indirectly to a malfunction of the molecular cross-talk between the nucleus and the mitochondria. This results in a decrease in the production of energy in the glia cells and thereby the beginning of demyelination. From another aspect, the presence of either the apolipoprotein E 2 or 4 alleles may cause an increased vulnerability to a slight chronic hypoperfusion of the white matter by reducing the range of mechanical and chemical flexibility of the glial cytoskeleton. In consequence of the chronic hypoperfusion, the functionally damaged kinesin protein gives rise also to the disturbances of the trafficking of the myelin basic protein mRNAs in the oligodendrocytes. On the basis of the current knowledge on LA, this article suggests a hypothetical molecular bridge between the genetic, biochemical, and clinical processes.",
author = "Z. Szolnoki",
year = "2007",
month = "2",
doi = "10.1385/NMM:9:1:21",
language = "English",
volume = "9",
pages = "21--34",
journal = "NeuroMolecular Medicine",
issn = "1535-1084",
publisher = "Humana Press",
number = "1",

}

TY - JOUR

T1 - Pathomechanism of leukoaraiosis

T2 - A molecular bridge between the genetic, biochemical, and clinical processes (a mitochondrial hypothesis)

AU - Szolnoki, Z.

PY - 2007/2

Y1 - 2007/2

N2 - Ischemic demyelination in the white matter of the brain is a frequent clinical entity. In neuroimaging terms, it is referred to as leukoaraiosis (LA). LA can reflect a broad public health problem, which is caused by a cognitive impairment ranging from mild slowness of thinking to full-blown subcortical dementia. One-quarter of subjects aged 65 yr or over are affected by some degree of white matter changes. There are a number of genetic factors that can be associated with circulatory disturbances of the white matter of the brain. A slight chronic hypoperfusion or an endothelial dysfunction associated with unfavorable genetic variations such as methylenetetrahydrofolate reductase C677T variation and angiotensin-converting enzyme I/D polymorphism then may lead indirectly to a malfunction of the molecular cross-talk between the nucleus and the mitochondria. This results in a decrease in the production of energy in the glia cells and thereby the beginning of demyelination. From another aspect, the presence of either the apolipoprotein E 2 or 4 alleles may cause an increased vulnerability to a slight chronic hypoperfusion of the white matter by reducing the range of mechanical and chemical flexibility of the glial cytoskeleton. In consequence of the chronic hypoperfusion, the functionally damaged kinesin protein gives rise also to the disturbances of the trafficking of the myelin basic protein mRNAs in the oligodendrocytes. On the basis of the current knowledge on LA, this article suggests a hypothetical molecular bridge between the genetic, biochemical, and clinical processes.

AB - Ischemic demyelination in the white matter of the brain is a frequent clinical entity. In neuroimaging terms, it is referred to as leukoaraiosis (LA). LA can reflect a broad public health problem, which is caused by a cognitive impairment ranging from mild slowness of thinking to full-blown subcortical dementia. One-quarter of subjects aged 65 yr or over are affected by some degree of white matter changes. There are a number of genetic factors that can be associated with circulatory disturbances of the white matter of the brain. A slight chronic hypoperfusion or an endothelial dysfunction associated with unfavorable genetic variations such as methylenetetrahydrofolate reductase C677T variation and angiotensin-converting enzyme I/D polymorphism then may lead indirectly to a malfunction of the molecular cross-talk between the nucleus and the mitochondria. This results in a decrease in the production of energy in the glia cells and thereby the beginning of demyelination. From another aspect, the presence of either the apolipoprotein E 2 or 4 alleles may cause an increased vulnerability to a slight chronic hypoperfusion of the white matter by reducing the range of mechanical and chemical flexibility of the glial cytoskeleton. In consequence of the chronic hypoperfusion, the functionally damaged kinesin protein gives rise also to the disturbances of the trafficking of the myelin basic protein mRNAs in the oligodendrocytes. On the basis of the current knowledge on LA, this article suggests a hypothetical molecular bridge between the genetic, biochemical, and clinical processes.

UR - http://www.scopus.com/inward/record.url?scp=33751075727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751075727&partnerID=8YFLogxK

U2 - 10.1385/NMM:9:1:21

DO - 10.1385/NMM:9:1:21

M3 - Article

C2 - 17114822

AN - SCOPUS:33751075727

VL - 9

SP - 21

EP - 34

JO - NeuroMolecular Medicine

JF - NeuroMolecular Medicine

SN - 1535-1084

IS - 1

ER -