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Wednesday 16 July 2003


Definition: Neurodegeneration is the progressive loss of structure or function ( degeneration ) of neurons, including death of neurons.

Many neurodegenerative diseases – including amyotrophic lateral sclerosis, Parkinson’s, Alzheimer’s, and Huntington’s – occur as a result of neurodegenerative processes.

Such diseases are incurable, resulting in progressive degeneration and/or death of neuron cells. As research progresses, many similarities appear that relate these diseases to one another on a sub-cellular level.

Neurodegeneration can be found in many different levels of neuronal circuitry ranging from molecular to systemic.

Neurodegenerative diseases

Neurodegenerative diseases typically involve deposits of inclusion bodies that contain abnormal aggregated proteins. Therefore, it has been suggested that protein aggregation is pathogenic.

However, several lines of evidence indicate that inclusion bodies are not the main cause of toxicity, and probably represent a cellular protective response. Aggregation is a complex multi-step process of protein conformational change and accretion.

The early species in this process might be most toxic, perhaps through the exposure of buried moieties such as main chain NH and CO groups that could serve as hydrogen bond donors or acceptors in abnormal interactions with other cellular proteins.


- paraneoplastic neurological degenerations


- Ross CA, Poirier MA. Opinion: What is the role of protein aggregation in neurodegeneration? Nat Rev Mol Cell Biol. 2005 Nov;6(11):891-8. PMID: 16167052

- Muchowski PJ, Wacker JL. Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci. 2005 Jan;6(1):11-22. PMID: 15611723

- Rao RV, Bredesen DE. Misfolded proteins, endoplasmic reticulum stress and neurodegeneration. Curr Opin Cell Biol. 2004 Dec;16(6):653-62. PMID: 15530777

- Wright AF, Jacobson SG, Cideciyan AV, Roman AJ, Shu X, Vlachantoni D, McInnes RR, Riemersma RA. Lifespan and mitochondrial control of neurodegeneration. Nat Genet. 2004 Nov;36(11):1153-8. PMID: 15514669

- Ross CA, Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med. 2004 Jul;10 Suppl:S10-7. PMID: 15272267

- Bossy-Wetzel E, Schwarzenbacher R, Lipton SA. Molecular pathways to neurodegeneration. Nat Med. 2004 Jul;10 Suppl:S2-9. PMID: 15272266

- Andersen JK. Oxidative stress in neurodegeneration: cause or consequence? Nat Med. 2004 Jul;10 Suppl:S18-25. PMID: 15298006

- Borsello T, Bonny C. Use of cell-permeable peptides to prevent neuronal degeneration. Trends Mol Med. 2004 May 1;10(5):239-244. PMID: 15121051

- Goedert M. Tau protein and neurodegeneration. Semin Cell Dev Biol. 2004 Feb;15(1):45-9. PMID: 15036206

- Albert ML, Darnell RB. Paraneoplastic neurological degenerations: keys to tumour immunity. Nat Rev Cancer. 2004 Jan;4(1):36-44. PMID: 14708025

- Mayeux R. Epidemiology of neurodegeneration. Annu Rev Neurosci. 2003;26:81-104. PMID: 12574495

- Kanazawa I. How do neurons die in neurodegenerative diseases? Trends Mol Med. 2001 Aug;7(8):339-44. PMID: 11516993

- Qian ZM, Shen X. Brain iron transport and neurodegeneration. Trends Mol Med. 2001 Mar;7(3):103-8. PMID: 11286780

- Kopito RR. Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol. 2000 Dec ;10(12):524-30. PMID : 11121744