**4.1 Parkinson's disease**

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons resulting in the deterioration of motor function. Altered expression of miR-133b has been reported in the midbrain of PD patients. This is notable as the transcription factor *Pitx3* is a target of miR-133b and is involved in the maturation and function of dopaminergic neurons [12]. Gain-of-function mutations to the leucine-rich repeat kinase 2 (LRRK2) has been closely associated with both sporadic and inherited forms of PD [72]. A reduction in miR-205 has been observed in sporadic PD patients with increased LRRK2 protein expression. Furthermore, *in vitro* studies revealed that miR-205 reduces LRRK2 expression and alleviates its neurodegenerative effect [73]. Conversely, LRRK2 has been shown to disrupt miR-187\* and let-7-mediated regulation of protein translation resulting in a pathogenic overproduction of E2F1/DP [74]. Another PD-related gene *SNCA* has been reported as a potential target of miR-7, miR-153 and miR-433 [75, 76]. miR-124 has been reported to play protective roles in dopaminergic neuronal apoptosis and autophagy in PD by regulating the AMPK/mTOR pathway. Suppression of miR-124 was been shown to regulate AMPK/mTOR signaling, significantly increasing p-AMPK activity and autophagy-associated Beclin 1 and LC3 II/LC3 I ratio [77].

In two independent studies, variations to the tsRNA-generating enzyme Ang have been reported in a subset of PD patients [78, 79]. Altered expression of tsRNA have also been reported in the amygdala [80], prefrontal cortex, cerebral spinal fluid and serum of PD patients [81]. Further work is required to elucidate the involvement of tsRNA in the pathogenesis of PD.
