Transmission of Diabetes Prion-Like Aggregates Triggers Disease Symptoms
Protein misfolding disorders (PMDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by the accumulation of misfolded protein aggregates in tissues including the brain. A few rare PMDs, such as bovine spongiform encephalopathy (BSE, or mad cow disease), and Creutzfeldt-Jacob Disease (CJD), can even be transmitted between humans or from animals to humans. In these cases, exposure to the causative misfolded protein aggregates, known as prions, triggers the transformation of normal proteins into the abnormal form. Effectively, prions "seed" the development of misfolded protein aggregation in the brain of the recipient, and this leads to the accumulation of toxic substances that destroy neurons.
Protein aggregation isn’t limited to the widely recognized PMDs, however. About 90% of patients with type 2 diabetes (T2D) develop pancreatic islet deposits of the peptide hormone islet amyloid polypeptide (IAPP). These misfolded protein aggregates start accumulating many years before the clinical diagnosis of T2D, explain Abhisek Mukherjee, Ph.D., and Claudio Soto, Ph.D., who head a research team at McGovern Medical School at The University of Texas Health Science Center at Houston that studies the molecular basis of PMDs, including AD, PD, and prion diseases.
Previous post mortem and animal studies have suggested that islet IAPP aggregation is linked with key T2D features, including the loss of beta cell mass, but the how these IAPP deposits cause disease development or progression isn’t yet understood. One Continue reading