Progress and Prospects in Parkinson's Research/Therapy/Neuroprotection/Phenylbutyrate

Phenylbutyrate is an approved drug used for treating urea-cycle disorders. It has recently been found to boost the expression of the DJ1 gene, reduce alpha-synuclein aggregation and more recently to attenuate the production of pro-inflammatory agents and reactive oxygen species by the microglia. This raises hopes that it may have therapeutic application in the control of the inflammation and oxidative stress that appear to be part of the pathogenetic processes in neurodegenerative diseases such as Parkinson's.

Research
2004

Gardian et al found that the application of phenylbutyrate to MPTP induced neurons reduced damage to the substantia nigra.

2011

Zhou et al found that In a transgenic mouse model of diffuse Lewy body disease, long-term administration of phenylbutyrate reduces α-synuclein aggregation in brain and prevents age-related deterioration in motor and cognitive function.

"We conclude that drugs that up-regulate DJ-1 gene expression may slow the progression of Parkinson disease by moderating oxidative stress and protein aggregation."

2012

Freed and Zhou have applied for funding to conduct an extended trial of phenylbutyrate.

Roy et al have demonstrated that Sodium Phenylbutyrate (NaPB) "'inhibits nigral expression of proinflammatory molecules and the activation of glial cells, increases the level antioxidant GSH in the [Substantia Nigra pars compacta], protects the loss of dopaminergic neurons, and improves the behavioral functions in MPTP-intoxicated mice. These results highlight undiscovered properties of NaPB and indicate that NaPB may be used for therapeutic intervention in PD or neurodegenerative disorders.'"