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Aggregates of TDP-43 protein spiral into view

In some neurodegenerative diseases, a protein called TDP-43 forms aggregates in the brain, resulting in neuronal cell death. The structure of these aggregates and their properties have been unveiled.
  1. Hana M. Odeh

    1. Hana M. Odeh is in the Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

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  2. James Shorter

    1. James Shorter is in the Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

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Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two devastating neurodegenerative diseases that share disease mechanisms and underlying genetics, and can co-occur in the same individual as ALS–FTLD. ALS is commonly characterized by the deterioration of the motor neurons that control movement, whereas FTLD is associated with the deterioration of neurons in a part of the brain called the cortex, leading to behavioural changes and memory loss. Unfortunately, there are no effective therapies for ALS and FTLD, and early diagnosis is challenging. A common hallmark of both conditions is the abnormal accumulation of a protein called TDP-43 inside degenerating neurons1–3. Writing in Nature, Arseni et al.4 report the structure of TDP-43 aggregates isolated from the brains of two individuals who had died from ALS–FTLD.

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Nature 601, 29-30 (2022)

doi: https://doi.org/10.1038/d41586-021-03605-0

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Competing Interests

J.S. is a consultant for Dewpoint Therapeutics, Vivid Sciences, ADRx, Korro Bio and Neumora.

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