Parkinson disease (PD) is a devastating neurodegenerative movement disorder, pathologically characterized by selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of intracytoplasmic inclusions named Lewy bodies and Lewy neurites (Schapira, Baillieres Clin. Neurol. 6:15-36, 1997). 1  Increasing numbers of genes have been identified as a genetic cause of PD (Hardy et al., Ann. Neurol. 60:389-398, 2006), for example, multiple missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene were recently found to be associated with an autosomal dominant form of familial PD (Paisan-Ruiz et al., Neuron 44:595-600, 2004; Zimprich et al., Neuron 44:601-607, 2004; Zabetian et al., Neurology 65:741-744, 2005). Recent genome-wide association studies (GWAS) also revealed LRRK2, together with SNCA (encoding alpha-syn) and PARK16, as shared risk loci for PD (Simon-Sanchez et al., Nat. Genet. 41:1308-1312, 2009; Satake et al., Nat. Genet. 41:1303-1307, 2009), indicating a potential contribution of normal LRRK2 protein to the etiology of sporadic PD cases. 0 

Micro-RNAs (miRNAs or miRs) are evolutionarily conserved small non-protein coding transcripts that bind to partially complementary binding sites in the 3? untranslated region (3?-UTR) of target messenger RNAs (mRNAs) and control the translation of their target mRNAs at the post-transcriptional level (Bartel, Cell 116:281-297, 2004). Several miRNAs have been associated with neurodegenerative disease as well as synaptic plasticity, memory formation and developmental cell fate decisions in the nervous system (Hebert and De Strooper, Trends Neurosci. 32:199-206, 2009; Kosik, Nat. Rev. Neurosci. 7:911-920, 2006). 0 

NIH inventors have recently discovered that LRRK2 protein expression is significantly increased in the brain of PD patients, while expression of miR-205 is specifically down-regulated in the same patients. Also, the NIH inventors have discovered that the expression levels of LRRK2 and miR-205 are dynamically regulated and reversely correlated in multiple brain regions and at different ages in mouse brains, indicating that miR-205 plays a regulatory role in LRRK2 protein expression. 1 

Based on these novel findings, the present technology provides for novel methods of treatment of patients suffering from PD disease by modulating the amount of miR-205 in patients by administration of a miR-205 gene product, a vector encoding a miR-205 gene product or an agent that increases expression of miR-205. The present technology also provides for methods of determining the effectiveness of different candidate drugs for the treatment of PD, methods of diagnosing PD, or having an increased susceptibility to developing PD, and an in vitro process for identifying a therapeutic agent for the treatment of PD. 0