Wednesday, October 7, 2015

heat shock protiens and parkinson's

HSP70 reduced a-syn, helping neurons survive. 

HSP70 reduced the larger oligomer's of a-syn in the extracellular space.
"αsyn between ∼440 and ∼65 kDa in size may be toxic αsyn species"
" Regardless, our data identify Hsp70 as one critical component in the defense against the toxic effects of extracellular misfolded αsyn in neurons."
"we cannot distinguish whether the observed actions of Hsp70 are mediated intracellularly, where an abundant supply of ATP exists, or extracellularly where ATP has been found following cellular stress (). It is also possible that Hsp70 works extracellularly and that ATP is not required, as was recently described"

Blocking HSP90 increased expression of HSP70. HSP104 also helps.

"Hsp104 has only limited ability to eliminate disordered aggregates and amyloid fibers implicated in human disease. Thus, we aim to engineer Hsp104 variants to reverse the protein misfolding implicated in neurodegenerative disorders."

HSPS can be up-regulated by heat and dehydration.  How to target HSP70 specifically?

Competitive exercise and work outdoors were better than other types of exercise, indicating maybe the extra heat was helping.

HSPS bind to ATP for some reason and are key to preventing misfolding.  The heat helps unbind proteins to reform.  Without heat stress, HSPS form 1 to 2% of total cellular proteins, and 4 to 6% when stressed.

torsinA acts like HSPs and is protective in flies, and its absence via mutation causes dystonia without neurodegeneration. 

Notes on heat bath:  105 F was about as high as I could stand. 20 minutes at 105 dropping to 100 F raised body temp to 101 F in 5 to 10 minutes. Heart rate would increase up to 120 BPM and more than this was not tolerable.  Lost 1 pound fluid in the 20 minutes (in 10 minutes is possible) and an  extra 0.3 pounds during cool down.  Have done baths and halogen-light bed to lose 6 pounds of water in 1 morning.

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