Promising Therapeutic Developments for TDP-Related Pathologies: Sílvia Porta, PhD

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“We have different types of pathology when we look at TDP-43 and different clinical symptomatology that can be also related with tau. On top of that, we have another level of complexity with genetic variants also playing a role in the disease. We are trying to see what is different between those cases, the signaling pathways, and the consequences of the patients that have different symptomatology.”

In various neurodegenerative disorders, such as Alzheimer disease (AD), the accumulation of TAR DNA-binding protein 43 (TDP-43) in cytoplasmic and intranuclear inclusions is a frequent cooccurring pathology. Despite our incomplete understanding of the direct mechanisms driving the progression of this disease and other neurological conditions, extensive research in this field has suggested a plausible model of progression in which misfolded proteins are released and exert their influence on recipient cells, potentially triggering the formation of new pathological aggregates.¹

Sílvia Porta, PhD, research assistant professor, pathology and laboratory medicine, University of Pennsylvania, presented new research in the perspectives session at the 2023 Alzheimer’s Association International Conference, July 16-20, in Amsterdam, the Netherlands. In the presentation, Porta noted that the research supports how various strains of TDP-43 could potentially influence the diverse manifestations of TDP-43 pathology in age-related dementias.¹

Porta recently sat down in an interview with NeurologyLive® during the meeting to discuss some of the common features among various neurological disorders related to TDP aggregation, and why it is gaining more attention in the research community. She also talked about how in vitro and in vivo models are being used in the lab to replicate brain conditions, and the insights they provide for therapeutic approaches. In addition, she spoke about the key findings and implications of developing TDP-targeting antibodies in reducing pathology.

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REFERENCES
1. Porta S. Biochemical and molecular heterogeneity of human TDP-43 proteinopathies in age-related dementias.Presented at: 2022 Alzheimer’s Association International Conference; July 16 to July 20; Amsterdam, the Netherlands.Abstract 75524.