Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend Life- and Healthspan.

Chronic, low-grade inflammation has been implicated in aging and age-dependent conditions, including Alzheimer's disease, cardiomyopathy, and cancer. One of the age-associated processes underlying chronic inflammation is protein aggregation, which is implicated in neuroinflammation and a broad spectrum of neurodegenerative diseases such as Alzheimer's, Huntington's, and Parkinson's diseases. We screened a panel of bioactive thiadiazolidinones (TDZDs) from our in-house library for rescue of protein aggregation in human-cell and models of neurodegeneration.

Aggregate Interactome Based on Protein Cross-linking Interfaces Predicts Drug Targets to Limit Aggregation in Neurodegenerative Diseases.

Diagnosis of neurodegenerative diseases hinges on "seed" proteins detected in disease-specific aggregates. These inclusions contain diverse constituents, adhering through aberrant interactions that our prior data indicate are nonrandom. To define preferential protein-protein contacts mediating aggregate coalescence, we created click-chemistry reagents that cross-link neighboring proteins within human, APP-driven, neuroblastoma-cell aggregates.

Apolipoprotein epsilon 3 alleles are associated with indicators of neuronal resilience.

Background: Epilepsy is associated with precocious development of Alzheimer-type neuropathological changes, including appearance of senile plaques, neuronal loss and glial activation. As inheritance of APOE ε4 allele(s) is reported to favor this outcome, we sought to investigate neuronal and glial responses that differ according to APOE genotype. With an eye toward defining ways in which APOE ε3 alleles may foster neuronal well-being in epilepsy and/or APOE ε4 alleles exacerbate neuronal decline, neuronal and glial characteristics were studied in temporal lobectomy specimens from epilepsy patients of either APOE ε4,4 or APOE ε3,3 genotype.