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A recent study explores the role of amyloidogenic evolvability in multiple sclerosis and multiple system atrophy, potentially unveiling novel intervention strategies for these chronic degenerative conditions.

  • Multiple sclerosis and multiple system atrophy, both characterized by impaired oligodendrocytes, may share a common mechanism through amyloidogenic evolvability.
  • The non-amyloidogenic homologue β-synuclein may modulate amyloidogenic evolvability, influencing the development of both diseases.
  • Understanding the role of amyloidogenic evolvability in oligodendrocyte diseases could lead to novel interventions for multiple sclerosis and multiple system atrophy.

Although multiple sclerosis (MS) and multiple system atrophy (MSA) are both characterized by impaired oligodendrocytes (OLs), their etiological relevance remains unclear. A recent study published in the journal Prion proposes a potential link between these two conditions through amyloidogenic evolvability (aEVO), a physiological function of amyloidogenic proteins (APs).

The Role of β-Synuclein in Amyloidogenic Evolvability

The non-amyloidogenic homologue β-synuclein (βS) may play a critical role in modulating aEVO. The study suggests that βS might decrease aEVO through a buffering action, promoting MS pathogenesis. Conversely, altered βS might increase aEVO, leading to oligodendrocyte degeneration and MSA development. It is proposed that βS, by associating with amyloidogenic proteins, may prevent the formation of toxic aggregates, thus influencing the development of both MS and MSA.

Therapeutic Strategies Targeting Amyloidogenic Evolvability

The concept of aEVO might provide insight into novel therapies for MS and MSA. By reducing βS expression, aEVO could be increased, potentially mitigating MS pathology and clinical symptoms. This could be achieved through antisense oligonucleotide (ASO) therapy or βS immunotherapy. For MSA, altered βS could be targeted to reduce disease progression, possibly through the use of emerging ASO therapy technologies or the development of specific immunotherapy. Manipulating βS expression through small interfering RNAs in cell culture models also shows promise.

Clinical Evidence and Future Directions

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The study acknowledges that its hypothesis requires further supporting experimental evidence. Nevertheless, exploring the role of aEVO in the pathogenesis of both MS and MSA could unveil new therapeutic targets and improve the understanding of the underlying mechanisms of these disorders. By targeting βS, it may be possible to develop combination therapies for MS that complement existing disease-modifying treatments, and to finally offer patients with MSA an effective disease-modifying intervention. 


Wei, J., Ho, G., Masliah, E., & Hashimoto, M. (2023). Differential involvement of amyloidogenic evolvability in oligodendropathies; Multiple Sclerosis and Multiple System Atrophy. Prion, 17(1), 29-34. https://doi.org/10.1080/19336896.2023.2172912