I'd like to speculatively propose a unified alzheimers hypothesis. The
TrpC5 calcium channel leaks free radicals into the blood brain barrier,
oligomerising prions. Trpc5 is the leakiest calcium channel and is mediated
by leptin, insulin and serotonin. Insulin ties into the idea that alzheimers
is typer 3 diabetes. Obesity and lack of sleep are also known to cause
leakage. The free radicals Fe/Cu/Zn have the same charge as Calcium and
produce bronsted acids which oligomerise amyloid and tau prions. Warfarin
and protom pump inhibitors have been implicated in alzheimers because of
calcium channels. I wonder if there is a similar chennel mediated by dopmine
instead of serotonin for parkinsons? I speculate if obsessives have
alzheimers and paranoids parkinsons? I would also like to speculate the
following therapeutic sequence: Rapamycin, Ketamine, Pyramidine, leptin, then
maintenance dantrolene and vitamin D.

From: vjp2@BioStrategist.com
Newsgroups: sci.med:556778 sci.med.diseases.osteoporosis:14103
Subject: Sun vs Alzheimers?
Date: Tue, 2 Aug 2016 00:59:39 +0000 (UTC)
Message-ID: <nnor9r$gfi$1@reader2.panix.com>

I attended a seminar by Stutzmann suggesting dantrolene and rapamycin as
Alzheimer treatment. A speculative jstor gedanken experiment that perhaps
too much sunless indoors causes modern prion neurodegenerative and other
aging diseases?

The pathogenesis of Alzheimers disease is it a lifelong "calciumopathy"?
Stutzmann GE. Neuroscientist. 2007 Oct;13(5):546-59. Recent studies in AD
models have identified marked dysregulations in calcium signaling and related
downstream pathways, which occur long before the diagnostic histopathological
or cognitive changes. Under normal conditions, intracellular calcium signals
are coupled to effectors that maintain a healthy physiological state.
Consequently, sustained up-regulation of calcium may have pathophysiological
consequences. Indeed, upon reviewing the current body of literature,
increased calcium levels are functionally linked to the major features and
risk factors of AD: ApoE4 expression, presenilin and APP mutations, beta
amyloid plaques, hyperphosphorylation of tau, apoptosis, and synaptic
dysfunction.

Dantrolene, A Treatment for Alzheimer's Disease? Li Liang, M.D.a,b and
Huafeng Wei, M.D., Ph.Da, Alzheimer Dis Assoc Disord. 2015 Jan-Mar; 29(1):
1-5. Previous studies support that the disruption of endoplasmic reticulum
(ER) Ca2+ via overactivation of Ryanodine receptors (RYRs) plays an important
role in the pathogenesis of AD. Normalization of intracellular Ca2+
homeostasis could be an effective strategy for AD therapies. Recent
preclinical studies consistently support the therapeutic effects of
dantrolene in various types of AD animal models.

Calcium channelopathies and Alzheimer's disease: insight into therapeutic
success and failures. Chakroborty S, Stutzmann GE. Eur J Pharmacol. 2014
Sep 15;739:83-95 Multifaceted involvement of calcium signaling in the
pathophysiology of Alzheimer's disease (AD), and summarize the various
therapeutic options currently available to combat this disease.

Genetic reduction of mammalian target of rapamycin ameliorates Alzheimer's
disease-like cognitive and pathological deficits by restoring hippocampal
gene expression signature. Caccamo A, De Pinto V, Messina A, Branca C, Oddo
S. J Neurosci. 2014 Jun 4;34(23):7988-98 Elevated mammalian target of
rapamycin (mTOR) signaling has been found in Alzheimer's disease (AD)
patients and is linked to diabetes and aging, two known risk factors for AD.

Novel mechanisms of calcium handling by the osteoclast Zaidi M1, Moonga
BS, Adebanjo OA. Proc Assoc Am Physicians. 1999 Jul-Aug;111(4):319-27. The
change in cytosolic Ca2+ is transduced finally into inhibition of bone
resorption. It has been shown that a type 2 ryanodine receptor isoform,
expressed uniquely in the plasma membrane, functions as a Ca2+ influx channel
and possibly as a Ca2+ sensor. Ryanodine receptors are ordinarily Ca2+
release channels that have a microsomal membrane location in a wide variety
of eukaryotic cells, including the osteoclasts.

Sunlight and vitamin D for bone health and prevention of autoimmune
diseases, cancers, and cardiovascular disease. Holick MF. Am J Clin
Nutr. 2004 Dec;80(6 Suppl):1678S-88S. Solar ultraviolet B photons are
absorbed by 7-dehydrocholesterol in the skin, leading to its transformation
to previtamin D3, which is rapidly converted to vitamin D3. Vitamin D
deficiency not only causes rickets among children but also precipitates and
exacerbates osteoporosis among adults and causes the painful bone disease
osteomalacia. Vitamin D deficiency has been associated with increased risks
of deadly cancers, cardiovascular disease, multiple sclerosis, rheumatoid
arthritis, and type 1 diabetes mellitus.

Association of coronary artery calcium with bone mineral density in
postmenopausal women. Xu R1, Ni Yang H, Li YQ, Wang QF, Guo AH, Ayiti A,
Chen XC, Gong R, Banu G, Dang Jian L, Gao Y, Sheng K, Maimti Y. Coron Artery
Dis. 2016 Jun 29 Atherosclerosis and osteoporosis (OP) are common diseases in
elderly individuals and may share common pathogenetic mechanisms. The aim of
this study was to investigate the association between bone mineral density
(BMD) and coronary artery calcium (CAC) inpostmenopausal women.

Suppression of glymphatic fluid transport in a mouse model of Alzheimer's
disease. Peng W, Achariyar TM, Li B, Liao Y, Mestre H, Hitomi E, Regan S,
Kasper T, Peng S, Ding F, Benveniste H, Nedergaard M, Deane R. Neurobiol
Dis. 2016 Sep;93:215-25 Importantly, glymphatic failure preceded significant
amyloid-? deposits, and thus, may be an early biomarker of AD. By extension,
restoring glymphatic inflow and ISF clearance are potential therapeutic
targets to slow the onset and progression of AD.

Sleep facilitates clearance of metabolites from the brain: glymphatic
function in aging and neurodegenerative diseases. Mendelsohn AR, Larrick JW.
Rejuvenation Res. 2013 Dec;16(6):518-23. Xie and colleagues now report that
in mice the clearance activity of this so-called "glymphatic system" is
strongly stimulated bysleep and is associated with an increase in
interstitial volume, possibly by shrinkage of astroglial cells. Moreover,
anesthesia and attenuation of adrenergic signaling can activate the
glymphatic system to clear potentially toxic proteins known to contribute to
the pathology of Alzheimer disease (AD) such as beta-amyloid
(Abeta). Clearance during sleep is as much as two-fold faster than during
waking hours.

Antibody against early driver of neurodegeneration cis P-tau blocks brain
injury and tauopathy. Kondo A, Shahpasand K, Mannix R, Qiu J, Moncaster J,
Chen CH, Yao Y, Lin YM, Driver JA, Sun Y, Wei S, Luo ML, Albayram O, Huang
P,Rotenberg A, Ryo A, Goldstein LE, Pascual-Leone A, McKee AC, Meehan W, Zhou
XZ, Lu KP. Nature. 2015 Jul 23;523(7561):431-6. Traumatic brain injury
(TBI), characterized by acute neurological dysfunction, is one of the best
known environmental risk factors for chronic traumatic encephalopathy and
Alzheimer's disease, the defining pathologic features of which include
tauopathy made of phosphorylated tau protein (P-tau). Treating TBI mice with
cis antibody blocks cistauosis, prevents tauopathy development and spread,
and restores many TBI-related structural and functional sequelae.

- = -
Vasos Panagiotopoulos, Columbia'81+, Reagan, Mozart, Pindus
blog: panix.com/~vjp2/ruminatn.htm - = - web: panix.com/~vjp2/vasos.htm
facebook.com/vasjpan2 - linkedin.com/in/vasjpan02 - biostrategist.com
---{Nothing herein constitutes advice. Everything fully disclaimed.}---