Visual Universitätsmedizin Mainz

Ralph A. Nixon, MD, PhD

Ralph_Nixon_sm.jpg

Professor of Psychiatry and Cell Biology
NYU Langone Medical Center

Director of The Center for Dementia Research
Nathan S. Kline Institute for Psychiatric Research, New York

Research

The Nixon lab focuses on the regulation of proteolytic processing and the control of protein export into axons and synapses, two aspects of neurobiology that govern the fate of normal and pathogenic proteins. They have identified dysfunction of the endosomal-lysosomal system, involving altered endocytosis and mistrafficking of proteases to endosomes, as the earliest known pathological response of neurons in Alzheimer’s disease. Further, they could show early endosomes to be major generators of the toxic b-amyloid peptide and implicate dysfunction of endosomes in the mechanism of b-amyloid accumulation in "sporadic" AD, the most common form of Alzheimer’s. Using genetic manipulations of proteolytic systems in mice as well cell culture models, their objective is to determine the consequences of endosomal-lysosomal and calpain system dysfunction on processing of Alzheimer-related proteins, receptor-mediated signal transduction as well as neuronal cell death pathways.

 

The Nixon Lab

Selected workshop-related publications

Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99).
Journal of Neuroscience. 3;39(27):5255-5268. doi: 10.1523/JNEUROSCI.0578-19.2019.
Jiang Y, Sato Y, Im E, Berg M, Bordi M, Darji S, Kumar A, Mohan PS, Bandyopadhyay U, Diaz A, Cuervo AM, Nixon RA. (2019)

Transgenic expression of a ratiometric autophagy probe specifically in neurons enables the interrogation of brain autophagy in vivo.
Autophagy. 15(3):543-557. doi: 10.1080/15548627.2018.1528812.
Lee JH, Rao MV, Yang DS, Stavrides P, Im E, Pensalfini A, Huo C, Sarkar P, Yoshimori T, Nixon RA. (2018)

Presenilin 1 Maintains Lysosomal Ca(2+) Homeostasis via TRPML1 by Regulating vATPase-Mediated Lysosome Acidification.
Cell Reports. 1;12(9):1430-44. doi: 10.1016/j.celrep.2015.07.050.
Lee JH, McBrayer MK, Wolfe DM, Haslett LJ, Kumar A, Sato Y, Lie PP, Mohan P, Coffey EE, Kompella U, Mitchell CH, Lloyd-Evans E, Nixon RA. (2015)

Selected Reviews

Lysosome trafficking and signaling in health and neurodegenerative diseases.
Neurobiology of Disease. 122:94-105. doi: 10.1016/j.nbd.2018.05.015.
Lie PPY, Nixon RA. (2019)

Amyloid precursor protein and endosomal-lysosomal dysfunction in Alzheimer's disease: inseparable partners in a multifactorial disease.
FASEB Journal 31(7):2729-2743. doi: 10.1096/fj.201700359.
Nixon RA. (2017)

Disorders of lysosomal acidification-The emerging role of v-ATPase in aging and neurodegenerative disease.
Ageing Research Reviews. 2016 Dec;32:75-88. doi: 10.1016/j.arr.2016.05.004.
Colacurcio DJ, Nixon RA. (2016)