New publication on mitochondrial dysfunction and Parkinson's disease

To date, several genes implicated in familial forms of Parkinson's disease (PD) have been reported, including PRKN (Parkin) involved in the regulation of mitochondrial function. Disruption of mitochondrial function has also been highlighted as a key mechanism of Parkinson's disease. The heterozygous variants in PRKN are common variants and may predispose to PD with highly reduced penetrance, through altered mitochondrial function.

Therefore, it is important to test for mitochondrial alteration in cells derived from carriers of pathogenic heterozygous variants to establish potential presymptomatic molecular markers.

In a study just published in Npj Parkinson’s disease, we generated lymphoblasts and human induced pluripotent stem cell (hiPSC)-derived neurons from non-manifesting heterozygous PRKN variant carriers and tested them for mitochondrial functionality.

We detected hyperactive mitochondrial respiration in lymphoblasts; hiPSC-derived neurons of non-manifesting heterozygous variant carriers also displayed several phenotypes of altered mitochondrial function.

The study results identify molecular phenotypes that might be used to monitor heterozygous PRKN variant carriers during the prodromal phase. Such markers might also be useful to identify individuals at greater risk of eventual disease development and for testing potential mitochondrial function-based neuroprotective therapies before neurodegeneration advances.

Parkinson´s disease (PD) is a neurodegenerative movement disorder, with both genetic and environmental factors playing an important role in disease onset, and age being the biggest risk factor for developing the disease. Parkinson´s disease is clinically characterized by cardinal motor manifestations, which are often preceded by non-motor symptoms for years or even decades. Even though most PD cases are classified as sporadic, a minority of cases (~10%) have a clear monogenic, autosomal dominant, or recessive, inheritance pattern. PRKN-linked PD is the most common form of early-onset PD across all ethnic groups, representing about 10–20% of cases with the age of onset from 40–50 years and up to 42.2% of cases with an age of onset ≤20 years.

Read the full article here: https://www.nature.com/articles/s41531-023-00499-9