Cellular Models of Neurodegeneration

TOPICAL COLLECTIONS

Guest Editors

Manu Sharma

Weill Cornell Medicine, Brain and Mind Research Institute

Manu Sharma, Ph.D. is an Assistant Professor of Neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine. He obtained his Ph.D. in Laboratory Medicine and Pathobiology from University of Toronto and the Hospital for Sick Children in Canada. For his thesis work he studied trafficking and turnover of the cystic fibrosis protein CFTR, and how its loss of function due to disease-related mutations can be rescued by small chemicals called chemical chaperones. As a post-doctoral fellow at UT Southwestern and Stanford University, he studied the function of two neurodegeneration-related synaptic proteins - alpha-synuclein and cysteine string protein-alpha. In 2014, he established his lab at Weill Cornell Medicine, where he aims to understand proteostasis mechanisms of aggregation-prone proteins which cause neurodegeneration in aging diseases such as Alzheimer’s disease and Parkinson’s disease.

Jacqueline Burré

Weill Cornell Medicine, Brain and Mind Research Institute

Jacqueline Burré, Ph.D. is an Assistant Professor of Neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine. She obtained her Ph.D. in Biochemistry from Goethe University in Germany, where she studied the make-up of synaptic vesicles, small lipid-protein particles within neurons that mediate neuronal communication. As a post-doctoral fellow at Stanford University, she pursued her interests in neuronal communication, focusing on the role of alpha-synuclein in normal brain function and in Parkinson’s disease. In 2014, she established her own research program at Weill Cornell Medicine, where she aims to determine the molecular mechanisms underlying diseases such as Parkinson’s disease, Alzheimer’s disease, and varied encephalopathies linked to mutations in Munc18-1/STXBP1, with a focus on the neuronal synapse. Her work has provided key insights into the normal function of disease-linked proteins in the brain, as well as into how dysfunction of these proteins contributes to neuropathology and disease. Ultimately, her goal is to identify rescue strategies, to overcome the deficits associated with dysfunction of these disease-linked proteins and the accompanying brain pathology.

Collection Overview

Neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia are devastating disorders with no known cure, mainly due to lack of understanding of the underlying disease mechanisms. Numerous mutant strains of mice have been generated as models to investigate these diseases. While fundamental insights into disease pathology and mechanism have been obtained, investigations at a subcellular resolution and high-throughput analyses such as drug screens are not feasible in animal models. Cellular model systems fill this niche. These systems have the advantage of addressing the underlying molecular and cellular disease mechanisms more acutely, enable fast and cost-effective genetic manipulations, and are ideal as a screening platform for libraries of new therapeutic compounds.

This methods collection includes a variety of cellular model systems to study neurodegenerative diseases, including yeast, non-neuronal models, primary neurons, and patient-derived neurons as 2D-induced neuron and 3D organoid cultures. Each model system has its particular strengths, for example, rapid genetic manipulation (yeast), active synapses (primary neurons), pure neuron types (induced neurons), and native-like neuronal connections and a glial milieu (organoids). Importantly, specific key aspects of neurodegenerative diseases have been reproduced in these cellular models, making them valuable for biochemical, cell biological, and high throughput studies, including those needed for early-stage drug discovery.