ALS Linked to Proteostatic Burden in Vulnerable Motor Neurons
Large motor neurons carry a hidden burden of degradation stress, worsened by loss of TDP-43 linked to ALS.
A defining feature of neurodegenerative disorders is selective neuronal vulnerability—why some neurons degenerate while others are spared.
Amyotrophic lateral sclerosis (ALS), an incurable neurodegenerative disorder, exemplifies disease-specific neuronal susceptibility as motor neurons responsible for muscle contraction undergo selective degeneration.
A new study published in Nature Communications uncovers some of the biology behind this process.
“Intrinsically accelerated cellular degradation is amplified by TDP-43 loss in ALS-vulnerable motor neurons in a zebrafish model”
The paper suggests that the cellular degradation load linked to cell size underlies motor neuron vulnerability and is a determinant of selective susceptibility in ALS.
The work highlights a target of therapy and prevention in the alleviation of catabolic stress.
Author's summary: ALS linked to cellular degradation in motor neurons.