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Lookup NU author(s): Professor Viktor KorolchukORCiD, Dr Tetsushi Kataura
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright © 2026 Kawachi, Kocak, Korolchuk, Kataura and Sarkar. Niemann-Pick type C1 (NPC1) disease is a neurodegenerative lysosomal storage disorder caused by loss-of-function mutations in the NPC1 gene. NPC1 deficit primarily disrupts lipid homeostasis and subsequently drives cellular degeneration through mechanisms involving impaired autophagy and mitophagy, mitochondrial dysfunction, and, recently demonstrated NAD depletion that links autophagy impairment to neuronal death. Emerging evidence also highlights the activation of innate immune signaling leading to neuroinflammation. In this review, we synthesize current mechanistic insights and describe how these molecular deficits are interconnected to drive neuronal death in NPC1 disease. We also discuss how these pathological processes parallel those observed in major age-related neurodegenerative pathologies such as Alzheimer’s and Parkinson’s disease. Finally, we highlight emerging therapeutic strategies that can potentially ameliorate these cellular deficits, offering avenues for mitigating neurodegeneration in NPC1 disease and other related neurodegenerative disorders.
Author(s): Kawachi Y, Kocak G, Korolchuk VI, Kataura T, Sarkar S
Publication type: Review
Publication status: Published
Journal: Frontiers in Neuroscience
Year: 2026
Volume: 20
Online publication date: 18/05/2026
Acceptance date: 05/05/2026
ISSN (print): 1662-4548
ISSN (electronic): 1662-453X
Publisher: Frontiers Media SA
URL: https://doi.org/10.3389/fnins.2026.1857866
DOI: 10.3389/fnins.2026.1857866
