α-Synuclein is colocalized with 14-3-3 and synphilin-1 in A53T transgenic mice

α-Synuclein is a major constituent of Lewy bodies, the neuropathological hallmark of Parkinson’s disease (PD). Three types of α-synuclein mutations, A53T, A30P, and E46K, have been reported in familial PD. Wild-type α-synuclein accumulates at high concentrations in Lewy bodies, and this process is accelerated with mutated A53T α-synuclein. The accumulation of α-synuclein is thought to be toxic, and causes neuronal death when α-synuclein aggregates into protofibrils and fibrils. Lewy bodies contain not only α-synuclein, but also other proteins including 14-3-3 proteins and synphilin-1. 14-3-3 Proteins exist mainly as dimers and are related to intracellular signal transduction pathways. Synphilin-1 is known to interact with α-synuclein, promoting the formation of cytoplasmic inclusions like Lewy bodies in vitro. To investigate the colocalization of α-synuclein, synphilin-1, and 14-3-3 proteins, we performed immunohistochemical studies on α-synuclein, 14-3-3 proteins, and synphilin-1 in the brain and spinal cord of A53T transgenic mice. In homozygous mouse brains, α-synuclein immunoreactivity was observed in the neuronal somata and processes in the medial part of the brainstem, deep cerebellar nuclei, and spinal cord. The distribution of 14-3-3 proteins and synphilin-1 immunoreactivity was similar to that of α-synuclein in the homozygous mice. Double immunofluorescent staining showed that α-synuclein and synphilin-1 or 14-3-3 proteins were colocalized in the pons and spinal cord. These results indicate that the accumulation of mutant α-synuclein occurs in association with 14-3-3 proteins and synphilin-1, and may cause the sequestration of important proteins including 14-3-3 proteins and synphilin-1. The sequestration and subsequent decrease in 14-3-3 proteins and synphilin-1 levels may account for neuronal cell death.