Differential involvement of amyloidogenic evolvability in oligodendropathies; Multiple Sclerosis and Multiple System...

Although multiple sclerosis (MS) and multiple system atrophy (MSA) are both characterized by impaired oligodendrocytes (OLs), the aetiological relevance remains obscure. Given inherent stressors affecting OLs, the objective of the present study was to discuss the possible role of amyloidogenic evolvability (aEVO) in these conditions. Hypothetically, in aEVO, protofibrils of amyloidogenic proteins (APs), including β-synuclein and β-amyloid, might form in response to diverse stressors in parental brain. Subsequently, the AP protofibrils might be transmitted to offspring via germ cells in a prion-like fashion. By virtue of the stress information conferred by protofibrillar APs, the OLs in offspring's brain might be more resilient to forthcoming stressors, perhaps reducing MS risk. aEVO could be comparable to a gene for the inheritance of acquired characteristics. On the contrary, during ageing, MSA risk is increased through antagonistic pleiotropy. Consistently, the expression levels of APs are reduced in MS, but are increased in MSA compared to controls. Furthermore, β-synuclein, the non-amyloidogenic homologue of β-synuclein, might exert a buffering effect on aEVO, and abnormal β-synuclein could also increase MS and MSA disease activity. Collectively, a better understanding of the role of aEVO in the OL diseases might lead to novel interventions for such chronic degenerative conditions.