Neuronal Cell Death Mechanisms in Major Neurodegenerative Diseases

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2018 Oct 12

PMID 30304824

Citations 161

Authors

Hao Chi

Hui-Yun Chang

Tzu-Kang Sang

Affiliations

Soon will be listed here.

Abstract

Neuronal cell death in the central nervous system has always been a challenging process to decipher. In normal physiological conditions, neuronal cell death is restricted in the adult brain, even in aged individuals. However, in the pathological conditions of various neurodegenerative diseases, cell death and shrinkage in a specific region of the brain represent a fundamental pathological feature across different neurodegenerative diseases. In this review, we will briefly go through the general pathways of cell death and describe evidence for cell death in the context of individual common neurodegenerative diseases, discussing our current understanding of cell death by connecting with renowned pathogenic proteins, including Tau, amyloid-beta, alpha-synuclein, huntingtin and TDP-43.

Citing Articles

The Role of tRNA-Derived Small RNAs (tsRNAs) in Regulating Cell Death of Cardiovascular Diseases.

Guo J, Chen X, Ren J, Wang Y, Wang K, Yang S Biology (Basel). 2025; 14(2).

PMID: 40001986 PMC: 11853139. DOI: 10.3390/biology14020218.

Gut microbiota: A new window for the prevention and treatment of neuropsychiatric disease.

Tang Y, Zhang Y, Chen C, Cao Y, Wang Q, Tang C J Cent Nerv Syst Dis. 2025; 17:11795735251322450.

PMID: 39989718 PMC: 11846125. DOI: 10.1177/11795735251322450.

Role of tau versus TDP-43 pathology on medial temporal lobe atrophy in aging and Alzheimer's disease.

Wisse L, Wuestefeld A, Murray M, Jagust W, La Joie R Alzheimers Dement. 2025; 21(2):e14582.

PMID: 39985478 PMC: 11846482. DOI: 10.1002/alz.14582.

Curcumin protects against MPP-induced neurotoxicity in SH-SY5Y cells by modulating the TRPV4 channel.

Cinar R, Yildizhan K Mol Biol Rep. 2025; 52(1):255.

PMID: 39976770 DOI: 10.1007/s11033-025-10345-1.

Promising Antidepressant Potential: The Role of Lactobacillus rhamnosus GG in Mental Health and Stress Response.

Isik M, Kose F, Ozbayer C, Budak O, Kaya R, Erdogan D Probiotics Antimicrob Proteins. 2025; .

PMID: 39962033 DOI: 10.1007/s12602-025-10470-0.

References

Masliah E, Mallory M, Alford M, Tanaka S, Hansen L . Caspase dependent DNA fragmentation might be associated with excitotoxicity in Alzheimer disease. J Neuropathol Exp Neurol. 1998; 57(11):1041-52. DOI: 10.1097/00005072-199811000-00007. View

Suhr S, Senut M, Whitelegge J, Faull K, Cuizon D, Gage F . Identities of sequestered proteins in aggregates from cells with induced polyglutamine expression. J Cell Biol. 2001; 153(2):283-94. PMC: 2169460. DOI: 10.1083/jcb.153.2.283. View

Pozo Devoto V, Dimopoulos N, Alloatti M, Pardi M, Saez T, Otero M . αSynuclein control of mitochondrial homeostasis in human-derived neurons is disrupted by mutations associated with Parkinson's disease. Sci Rep. 2017; 7(1):5042. PMC: 5506004. DOI: 10.1038/s41598-017-05334-9. View

McInnes J, Wierda K, Snellinx A, Bounti L, Wang Y, Stancu I . Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau. Neuron. 2018; 97(4):823-835.e8. DOI: 10.1016/j.neuron.2018.01.022. View

Tiwari M, Lopez-Cruzan M, Morgan W, Herman B . Loss of caspase-2-dependent apoptosis induces autophagy after mitochondrial oxidative stress in primary cultures of young adult cortical neurons. J Biol Chem. 2011; 286(10):8493-8506. PMC: 3048733. DOI: 10.1074/jbc.M110.163824. View

Nana A, Kim E, Thu D, Oorschot D, Tippett L, Hogg V . Widespread heterogeneous neuronal loss across the cerebral cortex in Huntington's disease. J Huntingtons Dis. 2014; 3(1):45-64. DOI: 10.3233/JHD-140092. View

Jodeiri Farshbaf M, Ghaedi K . Huntington's Disease and Mitochondria. Neurotox Res. 2017; 32(3):518-529. DOI: 10.1007/s12640-017-9766-1. View

Soto C . Unfolding the role of protein misfolding in neurodegenerative diseases. Nat Rev Neurosci. 2003; 4(1):49-60. DOI: 10.1038/nrn1007. View

Zhu X, Raina A, Perry G, Smith M . Apoptosis in Alzheimer disease: a mathematical improbability. Curr Alzheimer Res. 2006; 3(4):393-6. DOI: 10.2174/156720506778249470. View

10.

Andersen B, Gundersen H, Pakkenberg B . Aging of the human cerebellum: a stereological study. J Comp Neurol. 2003; 466(3):356-65. DOI: 10.1002/cne.10884. View

11.

Troncoso J, Sukhov R, Kawas C, Koliatsos V . In situ labeling of dying cortical neurons in normal aging and in Alzheimer's disease: correlations with senile plaques and disease progression. J Neuropathol Exp Neurol. 1996; 55(11):1134-42. DOI: 10.1097/00005072-199611000-00004. View

12.

Piccini A, Russo C, Gliozzi A, Relini A, Vitali A, Borghi R . beta-amyloid is different in normal aging and in Alzheimer disease. J Biol Chem. 2005; 280(40):34186-92. DOI: 10.1074/jbc.M501694200. View

13.

Magrassi L, Leto K, Rossi F . Lifespan of neurons is uncoupled from organismal lifespan. Proc Natl Acad Sci U S A. 2013; 110(11):4374-9. PMC: 3600460. DOI: 10.1073/pnas.1217505110. View

14.

Giannakopoulos P, Herrmann F, Bussiere T, Bouras C, Kovari E, Perl D . Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology. 2003; 60(9):1495-500. DOI: 10.1212/01.wnl.0000063311.58879.01. View

15.

Parkkinen L, OSullivan S, Collins C, Petrie A, Holton J, Revesz T . Disentangling the relationship between lewy bodies and nigral neuronal loss in Parkinson's disease. J Parkinsons Dis. 2013; 1(3):277-86. PMC: 4196643. DOI: 10.3233/JPD-2011-11046. View

16.

Armstrong R, Cairns N, Myers D, Smith C, Lantos P, Rossor M . A comparison of beta-amyloid deposition in the medial temporal lobe in sporadic Alzheimer's disease, Down's syndrome and normal elderly brains. Neurodegeneration. 1996; 5(1):35-41. DOI: 10.1006/neur.1996.0005. View

17.

Bano D, Ankarcrona M . Beyond the critical point: An overview of excitotoxicity, calcium overload and the downstream consequences. Neurosci Lett. 2017; 663:79-85. DOI: 10.1016/j.neulet.2017.08.048. View

18.

Tsuiji H, Inoue I, Takeuchi M, Furuya A, Yamakage Y, Watanabe S . TDP-43 accelerates age-dependent degeneration of interneurons. Sci Rep. 2017; 7(1):14972. PMC: 5668320. DOI: 10.1038/s41598-017-14966-w. View

19.

Rami A, Kogel D . Apoptosis meets autophagy-like cell death in the ischemic penumbra: Two sides of the same coin?. Autophagy. 2008; 4(4):422-6. DOI: 10.4161/auto.5778. View

20.

Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P . Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol. 2014; 15(2):135-47. DOI: 10.1038/nrm3737. View