Back to Search
Start Over
A mitochondrial basis for Huntington's disease: therapeutic prospects
- Source :
- Molecular and cellular biochemistry. 389(1-2)
- Publication Year :
- 2013
-
Abstract
- Huntington's disease (HD) is an autosomal dominant disease, with overt movement dysfunctions. Despite focused research on the basis of neurodegeneration in HD for last few decades, the mechanism for the site-specific lesion of neurons in the brain is not clear. All the explanations that partially clarify the phenomenon of neurodegeneration leads to one organelle, mitochondrion, which is severely affected in HD at the level of electron transport chain, Ca(2+) buffering efficiency and morphology. But, with the existing knowledge, it is not clear whether the cell death processes in HD initiate from mitochondria, though the Huntingtin (Htt) aggregates show close proximity to this organelle, or do some extracellular stimuli like TNFα or FasL trigger the process. Mainly because of the disparity in the different available experimental models, the results are quite confusing or at least inconsistent to a great extent. The fact remains that the mutant Htt protein was seen to be associated with mitochondria directly, and as the striatum is highly enriched with dopamine and glutamate, it may make the striatal mitochondria more vulnerable because of the presence of dopa-quinones, and due to an imbalance in Ca(2+). The current therapeutic strategies are based on symptomatic relief, and, therefore, mainly target neurotransmitter(s) and their receptors to modulate behavioral outputs, but none of them targets mitochondria or try to address the basic molecular events that cause neurons to die in discrete regions of the brain, which could probably be resulting from grave mitochondrial dysfunctions. Therefore, targeting mitochondria for their protection, while addressing symptomatic recovery, holds a great potential to tone down the progression of the disease, and to provide better relief to the patients and caretakers.
- Subjects :
- Genetics
Huntingtin
Cell Death
Clinical Biochemistry
Neurodegeneration
Autosomal dominant trait
Brain
Glutamic Acid
Nerve Tissue Proteins
Cell Biology
General Medicine
Biology
Mitochondrion
medicine.disease
Symptomatic relief
Mitochondria
DNM1L
Huntington Disease
Mitochondrial biogenesis
Huntington's disease
medicine
Animals
Humans
Molecular Biology
Neuroscience
Subjects
Details
- ISSN :
- 15734919
- Volume :
- 389
- Issue :
- 1-2
- Database :
- OpenAIRE
- Journal :
- Molecular and cellular biochemistry
- Accession number :
- edsair.doi.dedup.....d1256d5973897d12e0da731319223e84