Therapeutic Potential of α-Synuclein Evolvability for Autosomal Recessive Parkinson’s Disease

Figure 3

Schematic of the buffering effect of β- on αS evolvability (a) αS protofibrils might be involved in resistance against multiple stresses in parental brains. By virtue of information carried by transgenerational transmission of αS protofibrils in reproduction, offspring can cope with forthcoming stresses in the brain, otherwise leading to early degenerative diseases, including AR-PD. On the other hand, α-synucleinopathies, such as AD-PD and sPD, are later manifested through antagonistic pleiotropy mechanism in aging. Thus, αS evolvability acts as an inheritance of acquired characteristics that are evolutionally beneficial. βS might interact with αS and inhibit the aggregation of αS. As a result, βS might mitigate the neurotoxicity of αS and negatively regulate αS evolvability. (b) If expression of βS is too high, the aggregation of αS is inhibited and αS evolvability would be decreased. Consequently, the brain in offspring cannot obtain stress information enough to escape from developmental diseases. Instead, manifestation of neurodegenerative diseases may be less frequent in aging. (c) If expression of βS is too low, the aggregation of αS may be stimulated, and αS evolvability would be increased. As a result, neurodevelopmental diseases will be suppressed, whereas neurodegenerative diseases may later be manifested through the antagonistic pleiotropy mechanism in aging.

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