Apoptosis
Posted: Sun Jan 08, 2006 7:24 am
Ok...........the following pertains to Huntington's disease, but it also provides a short explanation with regard to apoptosis (which as we all know, we want to inhibit apoptosis in MS). And we all know how integral that Ca2 influx plays in axonal degeneration in MS, also.
Read the highlighted portions below and you will see how what they are saying also relates to apoptosis in MS.
(Hey...........blame Robin for getting me started here today. )
Deb
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Read the highlighted portions below and you will see how what they are saying also relates to apoptosis in MS.
(Hey...........blame Robin for getting me started here today. )
Deb
*************************
Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2602-7. Epub 2005 Feb 3. Related Articles, Links
Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease.
Tang TS, Slow E, Lupu V, Stavrovskaya IG, Sugimori M, Llinas R, Kristal BS, Hayden MR, Bezprozvanny I.
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Huntington's disease (HD) is caused by polyglutamine expansion (exp) in huntingtin. Here, we used a yeast artificial chromosome (YAC) transgenic mouse model of HD to investigate the connection between disturbed calcium (Ca2+) signaling and apoptosis of HD medium spiny neurons (MSN). Repetitive application of glutamate elevates cytosolic Ca2+ levels in MSN from the YAC128 mouse but not in MSN from the wild-type or control YAC18 mouse. Application of glutamate results in apoptosis of YAC128 MSN but not wild-type or YAC18 MSN. Analysis of glutamate-induced apoptosis of the YAC128 MSN revealed that (i) actions of glutamate are mediated by mGluR1/5 and NR2B glutamate receptors; (ii) membrane-permeable inositol 1,4,5-trisphosphate receptor blockers 2-APB and Enoxaparin (Lovenox) are neuroprotective; (iii) apoptosis involves the intrinsic pathway mediated by release of mitochondrial cytochrome c and activation of caspases 9 and 3; (iv) apoptosis requires mitochondrial Ca2+ overload and can be prevented by the mitochondrial Ca2+ uniporter blocker Ruthenium 360; and (v) apoptosis involves opening of mitochondrial permeability transition pore (MPTP) and can be prevented by MPTP blockers such as bongkrekic acid, Nortriptyline, Desipramine, Trifluoperazine, and Maprotiline. These findings describe a pathway directly linking disturbed Ca2+ signaling and degeneration of MSN in the caudate nucleus in HD. These findings also suggest that Ca2+ and MPTP blockers may have a therapeutic potential for treatment of HD.
PMID: 15695335 [PubMed - indexed for MEDLINE]