disease

A recent study showed that itanapraced disrupted genetic mutations associated with Parkinson’s disease and reduced loss of neurons in cell culture and mouse models. ImagesBazaar/Getty Images

• Mutations that enhance the activity of the LRRK2 enzyme are one of the most common mutations in inherited and sporadic Parkinson’s disease.
• A recent study showed that mutations that enhance the activity of the LRRK2 enzyme resulted in increased phosphorylation of a protein called amyloid precursor protein intracellular domain (AICD), which enhanced the expression of the LRRK2 gene.
• The use of itanapraced, a drug that inhibits AICD, disrupted this self-perpetuating cycle and attenuated the loss of neurons in cell culture and in mouse models of Parkinson’s disease.
• These findings suggest that itanapraced, a drug candidate for Alzheimer’s disease, could have the potential for the treatment of LRRK2-related Parkinson’s.

Mutations in the LRRK2 gene are the most common genetic cause of inherited and sporadic Parkinson’s disease (PD).

In particular, a specific mutation that increases the activity of the LRRK2 gene product is associated with 5–6% of inherited and 1–2% of sporadic cases of PD.

A recent study published in Science Signaling identified a novel mechanism through which mutations in LRRK2 may cause the loss of dopamine neurons in Parkinson’s disease.

The findings show that targeting this pathway or mechanism, using a drug candidate for treating Alzheimer’s disease (AD) in cell cultures and mice models of Parkinson’s disease, mitigated the loss of dopamine neurons.

One of the study’s senior authors, Zeng Li, Ph.D., principal investigator at the National Neuroscience Institute in Singapore, told Medical News Today:

“Mutant LRRK2 can promote the processing of APP into its transcriptionally active form, the APP intracellular domain (AICD). Here we showed that these proteins are linked in a self-perpetuating cycle. LRRK2-mediated phosphorylation of APP increased the abundance and activity of the AICD that then directly mediated LRRK2 transcription and LRRK2-mediated toxicity in Parkinson’s disease models. Our study unravels that AICD promotes LRRK2 expression to enable a feed-forward neurodegenerative mechanism in Parkinson’s disease.”