A review on pivotal genes in dopaminergic neurons life And its effects on Parkinson's disease

Parkinson’s disease is a neurodegenerative disorder. Dopaminergic neurons in the midbrain selectively degenerate during the course of the disease. This group of neurons are located in three distinct nuclei in the midbrain; substantia nigra pars compata(SNpc), ventral tegmental area(VTA) and retrorubral field. The development of these three nuclei is orchestrated by the expression of a set of transcription factors. Substantia nigra pars compata, Ventral tegmental area and retrorubral field have important roles in the control of movement and the and are involved in motivation,orgasm, cognition, drug addiction and psychiatric disorders.
The specific groups of genes which are pivotal to development of midbrain dopaminergic neurons are: Otx2, Gbx2, Pax2, En1, En2, Wnt1, Fgf8, Wnt5a, Foxa1 and Foxa2, SHH, Lmx1a and Lmx1b. These genes are essential in regional identity, fate determination, neuronal differentiation, postmitotic development and axon guidance of midbrain dopaminergic neurons. Several of the transcription factors also play a role in the survival and maintenance of the midbrain dopaminergic neurons throughout life.
Mutations or disorder in the expression of these genes would result in deficiency in the dopaminergic systems and/or mimicking the Parkinson’s disease-like symptoms in the animal models of the disease. A better understanding of the functional role of the developmental transcription factors may result in a deeper understanding of the physiology of the midbrain dopaminergic neurons and in development of novel gene therapeutic agents to to halt the process of neurodegeneration. The developmental transcription factors can also be utilized for achieving optimized in vitro protocols for differentiation of embryonic stem cells into midbrain dopaminergic neurons to be used for cell replacement therapy in Parkinson’s disease.