1-L Transcription in Parkinson's Disease.

Background: As a chronic degenerative disorder of the central nervous system that affects both motor and non-motor systems, Parkinson's disease (PD) is very complex, and explanations and models are needed to better understand how dopaminergic neurons are affected and microglia are activated.

Methods: A theoretical protein-RNA recognition code that assumes that the second letter in codons is compatible with specific amino acids involved in protein-RNA recognition was used to search for compatibility of human α-synuclein (α-syn) with mRNAs in the human transcriptome (1-L transcription).

Results: The 1-L transcription revealed compatible amino acid sequences with the ATTTA ARE (class I), PAS and polyA in α-syn, supporting a protein-RNA regulatory model. In PD, inflammatory microglia reactions, cognitive decline and motor circuit disturbances are observed. The model theoretically explains why α-syn producing neurons are less protected from inflammation and why microglia are activated. Consistent with knowledge of PD, the identified genes showed how the PI3K-AKT pathway is downregulated, how reactive oxygen species (ROS) production and sensitivity are increased, how mitochondria are destabilized, why autophagy is impaired, and why neuronal depigmentation is observed.

Conclusions: 1-L transcription of α-syn leads to genes/proteins relevant to PD. When α-syn is accepted as a small RNA recognition protein involved in the post-transcriptional regulations, some identified genes indicate that its function is an important regulatory factor associated with intracellular and extracellular transport of RNA vesicles. These vesicles are extremely important in cellular communication. In addition, the spectrum of identified genes strongly indicates that α-syn produced by neuronal cells is required for proper regulation of inflammatory and immune responses.