Our new paper on Parkinson’s disease

We observed selective downregulation of the novel PD risk factor RIT2 in vitro and in vivo. Rit2 overexpression in G2019S-LRRK2 cells rescued ALP abnormalities and diminished aSyn inclusions. In vivo, viral mediated overexpression of Rit2 operated neuroprotection against AAV-A53T-aSyn. Furthermore, Rit2 overexpression prevented the A53T-aSyn-dependent increase of LRRK2 kinase activity in vivo. On the other hand, reduction of Rit2 levels leads to defects in the ALP, similar to those induced by the G2019S-LRRK2 mutation. Our data indicate that Rit2 is required for correct lysosome function, inhibits overactive LRRK2 to ameliorate ALP impairment, and counteracts aSyn aggregation and related deficits. Targeting Rit2 could represent an effective strategy to combat neuropathology in familial and idiopathic PD.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting 2–3% of people over the age of 65. The disease is characterized by motor symptoms including resting tremor, rigidity, bradykinesia, and postural instability, which originate from the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Around 15% of PD patients have a family history and 5–10% of cases are caused by mutations and alterations in specific genes (e.g., SNCA, LRRK2, Parkin, VPS35).

Read the full article here: https://www.nature.com/articles/s41531-023-00484-2

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