Catalytic Cross Talk between Key Peptide Fragments That Couple Alzheimer's Disease with Amyotrophic Lateral Sclerosis.

Protein aggregation is a common feature in prominent neurodegenerative diseases, usually thought to be due to the assembly of a single peptide or protein. Recent studies have challenged this notion and suggested several proteins may be involved in promoting and amplifying disease. For example, the TDP-43 protein associated with Amyotrophic Lateral Sclerosis has been found in the brain along with Aβ assemblies associated with Alzheimer's disease, and those patients that show the presence of TDP-43 are 10 times more likely to demonstrate cognitive impairment compared to TDP-43-negative Alzheimer's patients.

Modulating ALS-Related Amyloidogenic TDP-43 Oligomeric Aggregates with Computationally Derived Therapeutic Molecules.

TDP-43 aggregates are a salient feature of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and a variety of other neurodegenerative diseases, including Alzheimer's disease (AD). With an anticipated growth in the most susceptible demographic, projections predict neurodegenerative diseases will potentially affect 15 million people in the United States by 2050. Currently, there are no cures for ALS, FTD, or AD.

Characterizing TDP-43 Oligomeric Assembly: Mechanistic and Structural Implications Involved in the Etiology of Amyotrophic Lateral Sclerosis.

Aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is a salient feature of amyotrophic lateral sclerosis (ALS), a debilitating neurodegenerative disorder affecting over 200 000 people worldwide. The protein undergoes both functional and pathogenic aggregation; the latter is irreversible and hypothesized to produce soluble oligomers that are toxic to neurons in addition to inclusions made of stable fibrous deposits. Despite progress made toward identifying disease-related proteins, the underlying pathogenic mechanism associated with these toxic oligomers remains elusive.