The role of mitochondrial dysfunction in HD has been under investigation. (medscape.com)
Quintanilla et al published the results of a study that focused on the contribution of mitochondrial dysfunction and transcriptional dysregulation to the pathogenesis of HD and the possibility of therapeutic intervention. (medscape.com)
Our project is important for determining whether the pre-clinical models generated by MJFF share potential mechanisms of neurodegeneration that have been implicated in human parkinsonism, such as mitochondrial dysfunction. (michaeljfox.org)
This research is important for guiding future therapeutic development based on targeting mitochondrial dysfunction in PD. (michaeljfox.org)
Because mitochondrial dysfunction has been implicated in Parkinson's disease and because several of these genes are believed to affect mitochondrial function, we analyzed the function of mitochondria in frozen brain tissue samples from the same wild-type and mutant pre-clinical models at age 8 months. (michaeljfox.org)
However, only frontal cortex tissue was available for analysis and it is possible that significant mitochondrial dysfunction occurs in the mutant pre-clinical models in the brains regions most affected in Parkinson's disease (the substantia nigra and the caudate/putamen). (michaeljfox.org)
This comprehensive review aims to concentrate on the potential neuroprotective agents that have demonstrated efficacy in addressing various pathogenic factors associated with neonatal HIBD, encompassing oxidative stress, calcium overload, mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory response, and apoptosis. (bvsalud.org)
while pink1 knoc ko ut ( ko ) rats have mitochondrial dysfunction, locomotor deficits, and \xce\xb1-synuclein aggregates in several brain regions such as cerebral cortex, dorsal striatum , and substantia nigra, the functional ramifications on synaptic circuits are unknown. (brain-knowledge-engine.org)
Several similarities have been observed between the endotoxemia pathway in heat stroke and ME/CFS, including vasoconstriction and hypoxia, gastrointestinal hyper-permeability and endotoxemia, oxidative and nitrosative stress and cytokine-associated inflammation, central nervous system dysfunction, coagulopathy dysfunction and endothelial cell injury, mitochondrial dysfunction, and altered gene expressions. (emerge.org.au)
There is evidence that metabolism of transmitter dopamine by monoamine oxidase enzyme may promote striatal damage in mitochondrial toxin induced models of Huntington's disease (HD) [ 4 ], and that HD is a devastating neurodegenerative disorder that reflect neuronal dysfunction and ultimately death in selected brain regions with striatum and cerebral cortex being the principal targets [ 5 ]. (biomedcentral.com)
Basal ganglia2
The muscle rigidity, tremor at rest, and slowness in initiation and execution of movement that are the cardinal motor symptoms of Parkinson's disease are attributed to a reduction in dopaminergic activity in the basal ganglia motor areas, particularly the putamen, due to gradually reduced innervation from the pars compacta of substantia nigra. (wikipedia.org)
We show that activity of the lysosomal hydrolase glucocerebrosidase gradually diminishes with age in the substantia nigra and putamen of healthy controls. (harvard.edu)
For example, relative to the rest of the human brain, the caudate, putamen and substantia nigra regions show an age-dependent increase in the heteroplasmy levels of the mtDNA 4977 deletion (a mutant genome harbouring a 4,977bp deletion) [ 8 ]. (biorxiv.org)
The direct pathway of the motor circuit is one in which projections from the cortex travel to the putamen directly to the internal segment of the globus pallidus (GPi also known as GP-Medial) or the substantia nigra, pars reticulata (SNr) and are then directed toward the ventral anterior nucleus (VA), and the ventral lateral nucleus of the thalamus (VL) and brainstem. (wikipedia.org)
adult male rhes ko mice showed a decrease in th and an increase in cd11b, both in the caudate putamen (cpu) and substantia nigra pars compacta (snc), and an increase in gfap in the cpu. (brain-knowledge-engine.org)
Oxidative phosphorylation1
COX is the fourth complex of the mitochondrial oxidative phosphorylation (OXPHOS) system where sequential electron transfer is coupled to proton pumping by complexes I-IV. (biomedcentral.com)
Neurodegeneration1
[ 2 ] All dementia share common molecular mechanisms responsible for disease etiology and progression, such as hypoxia and oxidative stress, neuroinflammation, mitochondrial bioenergetics, neurodegeneration, and blood-brain barrier permeability. (medscape.com)
Striatal2
In a similar study, treatment with pergolide for 6 weeks also showed no significant changes in [123I]β-CIT striatal, putamen, or caudate uptake, but an insignificant trend toward increased [123I]β-CIT uptake (Ahlskog et al. (top5binarybrokers.com)
Type I glutaric aciduria (GA1) results from mitochondrial matrix flavoprotein glutaryl-CoA dehydrogenase deficiency and is a cause of acute striatal necrosis in infancy. (omeka.net)
Neurons5
Disruptions in mitochondrial dynamics may contribute to the selective degeneration of dopamine (DA) neurons in Parkinson's disease (PD). (jneurosci.org)
However, little is known about the normal functions of mitochondrial dynamics in these neurons, especially in axons where degeneration begins, and this makes it difficult to understand the disease process. (jneurosci.org)
To study one aspect of mitochondrial dynamics-mitochondrial fission-in mouse DA neurons, we deleted the central fission protein dynamin-related protein 1 (Drp1). (jneurosci.org)
Drp1 is thus critical for targeting mitochondria to the nerve terminal, and a disruption in mitochondrial fission can contribute to the preferential death of nigrostriatal DA neurons. (jneurosci.org)
As neurons age, they show signs of diminished lysosomal and mitochondrial function, including increased oxidative stress and accumulation of misfolded proteins, and these changes become exacerbated PD. (harvard.edu)
The indirect pathway of the motor circuit is thought to project from the cortex, to the putamen, and to the thalamus and brainstem indirectly by passing through the external segment of the globus pallidus (GPe) then the subthalamic nucleus (STN) before looping back to the internal segment of the globus pallidus (GPi). (wikipedia.org)
Transcriptional1
We identified two major blood transcriptome types where type 1 was found more in men, the elderly, and overweight people and it upregulated genes associated with inflammation and increased heme metabolism, while type 2 was predominantly found in women, younger, and normal weight participants and it was associated with activated immune responses, transcriptional, ribosomal, mitochondrial, and telomere-maintenance cell-functions. (health-atlas.de)
Genome3
In multiple species, certain tissue types are prone to acquiring greater loads of mitochondrial genome (mtDNA) mutations relative to others, however the mechanisms that drive these heteroplasmy differences are unknown. (biorxiv.org)
We found that the conserved PTEN-induced putative kinase (PINK1/PINK-1) and the E3 ubiquitin-protein ligase parkin (PDR-1), which are required for mitochondrial autophagy (mitophagy), underlie stereotyped differences in heteroplasmy of a deleterious mitochondrial genome mutation (ΔmtDNA) between major somatic tissues types in Caenorhabditis elegans . (biorxiv.org)
Genetic testing for mitochondrial disorders using sequence analysis and deletion testing of the mitochondrial genome was negative and identified no pathogenic variant. (jmust.org)
SLC25A122
Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism. (neurotransmitter.net)
Two single nucleotide polymorphisms (SNPs) that showed evidence for divergent distribution between autistic and nonautistic subjects were identified, both within SLC25A12, a gene encoding the mitochondrial aspartate/glutamate carrier (AGC1). (neurotransmitter.net)
Lysosomal1
This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. (medscape.com)
Neurodegenerative1
Aside from her brother, the family genogram (Figure 3) revealed no significant illness that would indicate a mitochondrial or hereditary neurodegenerative disease, and all other half-siblings from both parents' first marriages showed no signs of neurologic disorder. (jmust.org)
Striatum1
The caudate nuclei and putamen, which are relatively similar structurally and functionally, are collectively known as the striatum. (suffernomore.com)
Underlie1
We will focus on measuring potential biochemical abnormalities in mitochondrial function and measuring potential neurochemical abnormalities in the levels or turnover of neurotransmitters such as dopamine and serotonin because these abnormalities likely underlie the clinical symptoms of PD. (michaeljfox.org)
Cytochrome2
SURF1 deficiency, a monogenic mitochondrial disorder, is the most frequent cause of cytochrome c oxidase (COX) deficient Leigh syndrome (LS). (biomedcentral.com)
5). Soluble gp120 activates oxidative stress and contributes to neuron cell death following mitochondrial permeabilization cytochrome C release and activation of caspases and endonucleases (6). (cell-signaling-pathways.com)
Nucleus2
to clarify the action of meth in 5-ht1b ko mice the effects of meth on extracellular levels of da (daec) and 5-ht (5-htec) in the caudate putamen (cpu) and the nucleus accumbens (nac) were examined. (brain-knowledge-engine.org)
mrna levels of mor1were significantly decreased in the caudate-putamen and nucleus accumbens of \xce\xb1-db ko compared to wt animals, but protein levels were unaltered. (brain-knowledge-engine.org)
Electron1
We did not observe significant differences between wild-type and mutant pre-clinical models in the activity of mitochondrial electron transport chain complex I, complex II, complex III or complex IV. (michaeljfox.org)
Disorder1
A prominent lactate doublet and decrease in absolute concentration of the NAA peak - findings consistent with a mitochondrial disorder, were seen. (jmust.org)
Diseases1
Due to their clinical and genetic heterogeneity, mitochondrial diseases are often a diagnostic challenge. (biomedcentral.com)
Carnitine1
Carnitine serves to transport fatty acids across mitochondrial membranes, thereby playing an important role in energy production and the metabolism of fatty acids. (suffernomore.com)
Brainstem1
His MRI/MRS (Figure 2) showed progressive symmetric widespread signal abnormalities involving the supratentorial and infratentorial compartments with predominant involvement of the brainstem, medial cerebellar hemisphere, and dorsal putamen bilaterally with parenchymal volume loss. (jmust.org)
Genetic1
2-4] Transmission is through mitochondrial, X-linked or autosomal recessive transmission,[5] however, the genetic cause of a number of Leigh syndrome cases remains unknown. (jmust.org)
Function2
Based on their findings, Quintanilla et al suggest the possibility that the effects of mutant HD can be reduced by increasing the availability and activity of PGC-1 α, a co-activator involved in mitochondrial function and glucose, lipid, and energy homeostasis, the function of which seems to be disrupted by mutant HD interactions that interfere with signaling pathways. (medscape.com)
2) these is impaired cross-modal function for vision/olfaction due to posterior putamen deficit. (nii.ac.jp)
Cell3
Drp1 loss rapidly eliminates the DA terminals in the caudate-putamen and causes cell bodies in the midbrain to degenerate and lose α-synuclein. (jneurosci.org)
The composition of the mitochondrial DNA (mtDNA) in each cell is in constant flux through processes of mutation, replication, and degradation. (biorxiv.org)
Launched inoculated stereotaxically into the rat caudate putamen (CP) SV(gp120) caused a partly hemorrhagic lesion in which neuron and other cell apoptosis continue for at least 12 weeks. (cell-signaling-pathways.com)
Important1
Heteroplasmy and mosaicism are therefore important determinants of mitochondrial disease pathophysiology. (biorxiv.org)