Signalling mechanisms underlying development and maintenance of dopamine neurons

Majority of the brain dopamine (DA) neurons reside in a distinct area in the midbrain and project axons into the striatum and frontal cortex to control central nervous system (CNS) functions such as movement, motivation and mood. Age-associated specific loss of DA neurons particularly in the midbrain region substantia nigra pars compacta (SNpc) causes Parkinson disease (PD), an incurable condition characterized by rigidity, involuntary and slowed movement affecting about 1% of people over the age of 60 years. Dopamine neurons appear to be one of the most sensitive types of neurons to both intrinsic and extrinsic stressors in the brain. Here we summarize how transcription factors, growth factors and in particular neurotrophic factors are used to make and maintain DA neurons. We also discuss mechanisms that underlie their specific vulnerability and highlight current state of art in drug development.