Invention:
This technology provides compounds and pharmaceutical compositions comprising small molecules that inhibit the formation of TAR DNA-binding protein 43 (TDP-43) condensates, which are protein aggregates linked to various neurodegenerative diseases including Alzheimer’s disease. By suppressing the formation of these aggregates, these molecules improve mitochondrial functionality. They hold promise as a targeted therapeutic intervention for many neurodegenerative diseases.
Background:
Alzheimer's disease (AD) is an age-associated neurodegenerative disorder with multifactorial etiology, intersecting genetic and environmental risk factors, and a lack of disease-modifying therapeutics. TAR DNA-binding protein 43 (TDP-43) is a highly conserved nuclear RNA/DNA-binding protein involved in the regulation of RNA processing. The accumulation of TDP-43 aggregates in the central nervous system is a common feature of many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and limbic predominant age-related TDP-43 encephalopathy (LATE). Accumulating evidence suggests that prion-like spreading of aberrant protein aggregates composed of tau, amyloid-β, and α-synuclein is involved in the progression of neurodegenerative diseases such as AD and PD. Similar to those of prion-like proteins, pathological aggregates of TDP-43 can be transferred from cell-to-cell in a seed-dependent and self-templating manner.
Applications:
- Neurodegenerative disorders and disease therapeutics
- Neurodegenerative disorders and disease research
Advantages:
- Novel approach to neurodegeneration
- No current drug targeting TDP-43
