. An aggregate-inducing peripherin isoform generated through intron retention is upregulated in amyotrophic lateral sclerosis and associated with disease pathology. J Neurosci. 2008 Feb 20;28(8):1833-40. PubMed.

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  1. Q&A with Jean-Pierre Julien. Questions by Esther Landhuis.

    Q: It seems that the idea that intermediate filaments are involved in ALS has gotten little attention. Why do you think this is the case?

    A: Previous transgenic mouse studies showed that overexpression of peripherin can provoke progressive motor neuron degeneration. The idea of intermediate filaments (IF) in ALS got some attention because of transgenic mouse studies showing that IF abnormalities can cause motor neuron disease. The concept that IFs might be involved in ALS is also appealing because IFs are abundant in large motor axons, and it would make sense that motor neurons might be vulnerable to cytoskeletal disorganization. However, the genetic screening has been disappointing. To date, only a few genetic variants in neurofilament NFH and peripherin genes have been reported in ALS patients, and it is unclear that these mutations are causative.

    Q: What is your perspective on this paper?

    A: It demonstrates that abnormal peripherin gene splicing does occur in sporadic ALS, and that the truncated P28 peripherin resulting from intron 3 and 4 retention can form aggregates. This is a very nice study. It is striking that the P28 protein is detected in ALS but not in controls. However, it remains unknown at this time to what extent the presence of this P28 protein might contribute to motor neuron degeneration in ALS. The results in Figure 5 of the paper indicate that this protein did not exhibit a high level of toxicity when expressed in cultured motor neurons. More work is needed to address this issue.

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