Unfortunately I cannot read the whole story, but this is what I have been talking earlier and Tanzi has published about cardiomyopathy. There will be need for the other 800 MPACs Prana has.
"Proteotoxicity and Cardiac Dysfunction — Alzheimer's Disease of the Heart?"
Monte S. Willis, M.D., Ph.D., and Cam Patterson, M.D., M.B.A.
N Engl J Med 2013; 368:455-464January 31, 2013DOI: 10.1056/NEJMra1106180
"Defective disposal of misfolded proteins is involved in the pathogenesis of neurodegenerative diseases, cystic fibrosis, and heart failure. Experimental studies suggest that therapies that target misfolded proteins may have broad clinical application".
Protein aggregates and novel presenilin gene variants in idiopathic dilated cardiomyopathy.
Gianni D, Li A, Tesco G, McKay KM, Moore J, Raygor K, Rota M, Gwathmey JK, Dec GW, Aretz T, Leri A, Semigran MJ, Anversa P, Macgillivray TE, Tanzi RE, del Monte F.
Cardiovascular Institute, Beth Israel Deaconess Medical Center, Boston, MA 02125, USA.
Heart failure is a debilitating condition resulting in severe disability and death. In a subset of cases, clustered as idiopathic dilated cardiomyopathy (iDCM), the origin of heart failure is unknown. In the brain of patients with dementia, proteinaceous aggregates and abnormal oligomeric assemblies of beta-amyloid impair cell function and lead to cell death.
METHODS AND RESULTS:
We have similarly characterized fibrillar and oligomeric assemblies in the hearts of iDCM patients, pointing to abnormal protein aggregation as a determinant of iDCM. We also showed that oligomers alter myocyte Ca(2+) homeostasis. Additionally, we have identified 2 new sequence variants in the presenilin-1 (PSEN1) gene promoter leading to reduced gene and protein expression. We also show that presenilin-1 coimmunoprecipitates with SERCA2a.
On the basis of these findings, we propose that 2 mechanisms may link protein aggregation and cardiac function: oligomer-induced changes on Ca(2+) handling and a direct effect of PSEN1 sequence variants on excitation-contraction coupling protein function.