interestingtome1 • Jun 6, 2015 12:05 PM Remove 4users liked this postsusers disliked this posts2Reply
Degradation of misfolded proteins by autophagy: is it a strategy for Huntington's disease treatment?
This paper doesn't mention metals but gets to the viability of treatment of HD with drugs that can act on the mHtt - something which was observed using PBT2 with Reach2HD participants.
J Huntingtons Dis. 2013
Degradation of misfolded proteins by autophagy: is it a strategy for Huntington's disease treatment?
Lin F, Qin ZH.
Abstract
Autophagy is a degradation pathway for long-lived cytoplasmic proteins, protein complexes, or damaged organelles. The accumulation and aggregation of misfolded proteins are hallmarks of several neurodegenerative diseases. Many researchers have reported that autophagy degrades disease-causing misfolded and aggregated proteins, including mutant huntingtin (Htt) in Huntington's disease, mutant synuclein in familial Parkingson's disease, mutant Cu, Zn-Superoxide dismutase (SOD1) in familial amyotrophic lateral sclerosis. In this review, we will bring up new evidence to elucidate the involvement of autophagy in degradation of mutant Htt, discuss the mechanisms regulating the degradation of mutant Htt by autophagy and the therapeutic effects of drugs that enhance autophagy to improve clearance of mutant Htt. We propose that enhancement of autophagy by drugs may be a strategy to treat or #$%$ progression of Huntington's disease.
Follow on by Kad
Clioquinol induces autophagy in cultured astrocytes and neurons by acting as a zinc ionophore
Mi-Ha Park a,b, Sook-Jeong Lee b, Hyae-ran Byun b, Yunha Kim d, Young J. Oh a, Jae-Young Koh b,c,, Jung Jin Hwang d,
a Department of Biology, University of Yonsei, College of Life Science and Biotechnology, Seoul 120-749, Republic of Korea
b Neural Injury Research Lab, University of Ulsan, College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea
c Department of Neurology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea
d Institute for Innovative Cancer Research, University of Ulsan, College of Medicine, Asan Medical Center, Seoul 138-736, Republic of Korea
This Korean work leaves little doubt an MPAC can clear Htt.
[ Moreover, astrocytes and SH-SY5Y cells expressing mutant huntingtin (mHttQ74) accumulated less aggregates when treated with clioquinol, and this effect was reversed by TPEN. These results indicate that clioquinol-induced autophagy is likely to be physiologically functional.
The present study demonstrates that clioquinol induces autophagy in a zinc-dependent manner and contributes to clearance of aggregated proteins in astrocytes and neurons. Hence, in addition to its metal-chelating effect in and around amyloid beta (Aβ) plaques, clioquinol may contribute to the reduction of Aβ loads by activating autophagy by increasing or normalizing intracellular zinc]
It said accumulates less. My take is the earlier the MPAC can hit the problem, the higher the chances of clearance assistance to boost to the brains own clearance mechanisms back into control. This research clearly demonstrates an MPAC can clear Htt. The shift in the Htt signal in the Reach2HD trial suggests this happened in humans. The drug was more effective in very early sympomatic patients. It has a proven safety record. Perhaps at risk patients in danger of converting to symptomatic should be given access to this drug ASAP,or yesterday
For anyone new to this, Prana first trialled PBT1, which is clioquinol. There were some safety issues and low BBB(Blood Brain Barrier) penetration. PBT2 was developed with many times the ability of CQ to pass the BBB and a better safety profile. PBT2 is an analog of CQ
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interestingtome1 • Jun 6, 2015 12:05 PM Remove 4users liked this...
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