Taking the parkin brakes off of neuronal NLRP3 drives inflammasome activation and neurodegeneration in Parkinson's disease

Article Neurosciences

Neuronal NLRP3 is a parkin substrate that drives neurodegeneration in Parkinson's disease

Nikhil Panicker et al.

Summary: Parkinson's disease is caused by alpha-synuclein accumulation and death of dopamine neurons in the substantia nigra pars compacta, with NLRP3 inflammasome hyperactivation playing a role in the disease. Loss of parkin activity leads to spontaneous assembly of NLRP3 inflammasome in dopamine neurons, which is further exacerbated by mitochondrial-derived reactive oxygen species. Inhibition of neuronal NLRP3 inflammasome assembly can prevent degeneration of dopamine neurons in PD models.

NEURON (2022)

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Review Cell Biology

The cell biology of Parkinson's disease

Nikhil Panicker et al.

Summary: Parkinson's disease is a progressive neurodegenerative disorder caused by the death of dopamine neurons in the substantia nigra pars compacta. Genes involved in rare, inheritable forms of PD, such as PARK genes, encode proteins that play key roles in the pathology and neuroprotective mechanisms of the disease. Understanding the cellular and non-cell-autonomous pathways involved in PD is crucial for developing therapies to slow or halt its progression.

JOURNAL OF CELL BIOLOGY (2021)

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Review Clinical Neurology