Northwestern University Feinberg School of Medicine

Mazzulli Laboratory

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 and 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:

Feinberg News link

PNAS link

Protein misfolding in Parkinson's and development of a new combination therapy:

Feinberg News link

Neuron link

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

  

Selected Publications

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.

View all Publications

Joseph R Mazzulli, PhD

Joseph R Mazzulli, PhD
Associate Professor in the Ken and Ruth Davee Department of Neurology


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