Lysosomal diseases are a family of over 50 disorders caused by defects in proteins critical for normal function of the endosomal/lysosomal system and characterized by complex pathogenic cascades involving progressive dysfunction of many organ systems, most notably the brain. Evidence suggests that compromise in lysosomal function is highly varied and leads to changes in multiple substrate processing and endosomal signalling, in calcium homoeostasis and endoplasmic reticulum stress, and in autophagocytosis and proteasome function. Neurons are highly vulnerable and show abnormalities in perikarya, dendrites and axons, often in ways seemingly unrelated to the primary lysosomal defect. A notable example is NAD (neuroaxonal dystrophy), which is characterized by formation of focal enlargements (spheroids) containing diverse organelles and other components consistent with compromise of retrograde axonal transport. Although neurons may be universally susceptible to NAD, GABAergic neurons, particularly Purkinje cells, appear most vulnerable and ataxia and related features of cerebellar dysfunction are a common outcome. As NAD is found early in disease and thus may be a contributor to Purkinje cell dysfunction and death, understanding its link to lysosomal compromise could lead to therapies designed to prevent its occurrence and thereby ameliorate cerebellar dysfunction.
Skip Nav Destination
Article navigation
December 2010
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
November 24 2010
Lysosomal compromise and brain dysfunction: examining the role of neuroaxonal dystrophy
Steven U. Walkley;
Steven U. Walkley
1
*Department of Neuroscience, Rose F. Kennedy Center, Albert Einstein College of Medicine, Bronx, NY 10461, U.S.A.
1To whom correspondence should be addressed (email steve.walkley@einstein.yu.edu).
Search for other works by this author on:
Jakub Sikora;
Jakub Sikora
†Institute of Inherited Metabolic Diseases, 1st Faculty of Medicine, Charles University in Prague, 128 08 Prague 2, Czech Republic
Search for other works by this author on:
Matthew Micsenyi;
Matthew Micsenyi
*Department of Neuroscience, Rose F. Kennedy Center, Albert Einstein College of Medicine, Bronx, NY 10461, U.S.A.
Search for other works by this author on:
Cristin Davidson;
Cristin Davidson
*Department of Neuroscience, Rose F. Kennedy Center, Albert Einstein College of Medicine, Bronx, NY 10461, U.S.A.
Search for other works by this author on:
Kostantin Dobrenis
Kostantin Dobrenis
*Department of Neuroscience, Rose F. Kennedy Center, Albert Einstein College of Medicine, Bronx, NY 10461, U.S.A.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
April 26 2010
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem Soc Trans (2010) 38 (6): 1436–1441.
Article history
Received:
April 26 2010
Citation
Steven U. Walkley, Jakub Sikora, Matthew Micsenyi, Cristin Davidson, Kostantin Dobrenis; Lysosomal compromise and brain dysfunction: examining the role of neuroaxonal dystrophy. Biochem Soc Trans 1 December 2010; 38 (6): 1436–1441. doi: https://doi.org/10.1042/BST0381436
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.