- Platt Laboratory | Lysosomal and Sphingolipid Disorders Research Group
My work focuses on lysosomal dysfunction and glycosphingolipid dysregulation in rare and common neurodegenerative diseases.
Historically, the early-onset rare neurodegenerative lysosomal storage disorders (LSDs) have been studied as discrete metabolic diseases in their own right. However, in recent years some unanticipated and exciting links with common late-onset neurodegenerative diseases, like Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), have emerged.
Recent reports show changes in glycosphingolipid (GSL) levels in these more common neurodegenerative disorders. However, the relationship between basic biochemical mechanisms like lysosomal dysfunction and lipid dysregulation in ALS and PD remains poorly understood.
In this project, I am now investigating the basic biological processes causing GSL changes and lysosomal dysfunction in these diseases.
- Lysosomal dysfunction in PD and ALS
- Glycosphingolipid dysregulation in PD and ALS
- Evaluation of the effects of lipid-targeted therapies in rare and more common diseases
- Identification of novel lipid-related biomarkers before onset of disease
This work is supported by Parkinson’s disease UK and Spedding Research Solutions SARL, France.
N-Butyl-l-deoxynojirimycin (l-NBDNJ): Synthesis of an Allosteric Enhancer of α-Glucosidase Activity for the Treatment of Pompe Disease.
D'Alonzo D. et al, (2017), J Med Chem, 60, 9462 - 9469
Development of gene therapy for Niemann-Pick Type C disease
Hughes M. et al, (2017), HUMAN GENE THERAPY, 28, A15 - A15
Inhibition of β-Glucocerebrosidase Activity Preserves Motor Unit Integrity in a Mouse Model of Amyotrophic Lateral Sclerosis.
Henriques A. et al, (2017), Sci Rep, 7
Amyotrophic lateral sclerosis and denervation alter sphingolipids and up-regulate glucosylceramide synthase.
Henriques A. et al, (2015), Hum Mol Genet, 24, 7390 - 7405