Fig. 8

The hypothetical scheme of the process of Lewy body formation in PLA2G6-associated neurodegeneration (PLAN). a Normal mitochondrion. b αSyn/PαSyn accumulates at the damaged mitochondrial membrane with PLA2G6 dysfunction. c High expression of αSyn/PαSyn stabilizes the mitochondrial membrane. d Due to the high affinity of αSyn for damaged mitochondrial membranes, mitochondria loaded with αSyn/PαSyn are clustered. e The cluster of the damaged mitochondria forms a small inclusion that contains toxic materials inside. f The small inclusion becomes large to be a Lewy body (LB), which boundary is formed by αSyn/PαSyn and mitochondrial membrane components. g When the boundary, which is sufficiently strong to sequester toxic materials inside, the LB-bearing neuron survives for a long time. h When this boundary breaks down, pro-apoptotic materials are released into the neuron, leading to rapid neuronal death. The image of neurons double-stained with immunohistochemistry for PαSyn (in brown) and tyrosine hydroxylase (in blue) is taken from the locus coeruleus of a patient with PLAN in (g), and a patient with PD in (h)