Pathways to the LysosomeDiscovering new pathways to improve lysosomal function in neurodegenerative proteinopathiesPathways to the LysosomeDiscovering new pathways to improve lysosomal function in neurodegenerative proteinopathies
Models of Neuronal AgingWe study age-dependent pathological changes in patient-derived neurons by culturing for hundreds of days in vitro to model chronic neurodegenerative diseasesModels of Neuronal AgingWe study age-dependent pathological changes in patient-derived neurons by culturing for hundreds of days in vitro to model chronic neurodegenerative diseases
ProteotoxicityOur goal is to understand the relationship between amyloid formation and neurotoxicity to uncover new therapeutic targets for neurodegenerative diseasesProteotoxicityOur goal is to understand the relationship between amyloid formation and neurotoxicity to uncover new therapeutic targets for neurodegenerative diseases
About Our Lab
The Mazzulli Lab is interested in determining how protein misfolding and amyloid formation results in cell death. Many chronic neurodegenerative disorders such as Parkinson’s disease, and Lewy body related dementias are characterized by the accumulation of misfolded proteins within the nervous system. We use patient neurons derived from induced pluripotent stem cells (iPSC) coupled with analytic biochemical techniques to study protein accumulation and lysosomal clearance mechanisms.
News and Events
Phenotypic variability in Gaucher's disease and link to Parkinson's:
Protein misfolding in Parkinson's and development of a new combination therapy:
Lysosome enhancement as a therapeutic strategy:
AlzForum: Small Molecules Liven Up Lethargic Lysosomes in Parkinson’s Neurons
The Scientist: Lysosomal Links to Parkinson's Disease
Batten's Disease:
Selected Publications
Pitcairn C, et al, Impaired autophagic-lysosomal fusion in Parkinson's patient midbrain neurons occurs through loss of ykt6 and is rescued by farnesyltransferase inhibition, J. Neurosci,2023 Feb 13 PMID: 36788031
Stojkovska I, et al, Rescue of α-synuclein aggregation in Parkinson’s patient neurons by synergistic enhancement of ER proteostasis and protein trafficking, Neuron, 2022 Feb 2;110(3):436-451. PMID: 34793693
Fredriksen, K. et al. Pathological a-syn aggregation is mediated by glycosphingolipid chain length and the physiological state of a-synuclein in vivo. Proc Natl Acad Sci U S A Dec 14th,2021. PMID:34893541
Cuddy LK, et al. Stress-Induced Cellular Clearance Is Mediated by the SNARE Protein ykt6 and Disrupted by α-Synuclein. Neuron, 2019, Dec 4;104(5):869-884.e11. doi: 10.1016/j.neuron.2019.09.001., PMID: 31648898
Zunke F, et al. Reversible Conformational Conversion of α-Synuclein into Toxic Assemblies by Glucosylceramide. Neuron, Jan 3rd, 2018. 97(1), 92-107e10. PMID:29290548
Mazzulli JR, et al. Activation of b-Glucocerebrosidase Reduces Pathological a-Synuclein and Restores Lysosomal Function in Parkinson’s Patient Midbrain Neurons, J. Neurosci, Jul 20, 2016. 36(29):7693-706. PMID: 27445146
Mazzulli JR, et al. α-Synuclein-induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models. PNAS, Feb 2, 2016. 113(7):1931-6. PMID: 26839413
Mazzulli JR, et al. Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell. July 2011; 146, 37-52. PMID: 21700325.
