Background pattern of a brain with neural connections

Team Hardy

Dissecting the Mechanisms Underlying Disease Progression in Parkinsonism

2020-Present

We want to find and understand the genes that are involved in Parkinson’s progression and test whether modulating them pharmacologically influences disease progression. Through genetic analysis, we will find genes that influence the progression of parkinsonism, and then assess the mechanisms by which they affect disease development. We have already found that GBA and LRRK2 influence clinical rates of decline so we will test, in a mouse model of pathology progression, whether inhibiting these enzymes influences pathology spread and thereby develop a relevant platform to test drugs for slowing disease progression.

Tags
Alpha-synuclein Animal models Clinical measures Genetic targets Glycosphingolipids Lysosomes Mitophagy Pathology

Leadership

John Hardy

John Hardy

Lead PI (Core Leadership)

Zane Jaunmuktane

Zane Jaunmuktane

Co-PI (Core Leadership)

Frances Platt

Frances Platt

Co-PI (Core Leadership)

Mina Ryten

Mina Ryten

Co-PI (Core Leadership)

Maria Grazia Spillantini

Maria Grazia Spillantini

Co-PI (Core Leadership)

June Smalley

June Smalley

Project Manager

Project Highlights

GPNMB is a biomarker for lysosomal dysfunction and is secreted via LRRK2-modulated lysosomal exocytosis

Genome-wide association studies have identified *Glycoprotein Nmb* (*GPNMB*) as a risk factor for Parkinson’s Disease. The risk allele increases *GPNMB* transcription and GPNMB protein levels in the CSF highlighting GPMNB as a potential biomarker for Parkinson’s Disease. However, a lack of knowledge of GPNMB’s function and mechanism of secretion have hindered an interpretation of...

Contributions

Here is an overview of how this team’s article findings have contributed to the PD field as of June 2025. There are two different categorizations of these contributions – one by impact to the PD community and a second by scientific category.

Impact

Category

Accolades

Members of the team have been recognized for their contributions.

Team Hardy

Open Science Champions

Alejandro Martinez-Carrasco, Regina Reynolds, Mina Ryten, Oke Avwenagha, Raquel Real, Karishma D’Sa

Network Spotlights

Oke Avwenagha, Zane Jaunmuktane, Toby Curless, Benjamin O’Callaghan, Raquel Real, Sonia Garcia-Ruiz, Oke Avwenagha, Maryam Shoai, Aine Fairbrother-Browne

In the News

Updates will be posted when available.

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