These authors contributed equally to this study.
Tracking extranigral degeneration in animal models of Parkinson’s disease: quest for effective therapeutic strategies
Article first published online: 17 JUN 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 118, Issue 3, pages 326–338, August 2011
How to Cite
Knaryan, V. H., Samantaray, S., Le Gal, C., Ray, S. K. and Banik, N. L. (2011), Tracking extranigral degeneration in animal models of Parkinson’s disease: quest for effective therapeutic strategies. Journal of Neurochemistry, 118: 326–338. doi: 10.1111/j.1471-4159.2011.07320.x
- Issue published online: 12 JUL 2011
- Article first published online: 17 JUN 2011
- Accepted manuscript online: 26 MAY 2011 11:22AM EST
- Received February 22, 2011; revised manuscript received May 23, 2011; accepted May 24, 2011.
- animal models;
- extranigral degeneration;
- Parkinson’s disease;
- spinal cord degeneration
J. Neurochem. (2011) 118, 326–338.
Sporadic Parkinson’s disease (PD) is now interpreted as a complex nervous system disorder in which the projection neurons are predominantly damaged. Such an interpretation is based on mapping of Lewy body and Lewy neurite pathology. Symptoms of the human disease are much widespread, which span from pre-clinical non-motor symptoms and clinical motor symptoms to cognitive discrepancies often seen in advanced stages. Existing symptomatic treatments further complicate with overt drug-irresponsive symptoms. PD is better understood by assimilation of extranigral degenerative pathways with nigrostriatal degenerative mechanisms. The term ‘extranigral’ appeared first in the 1990s to more rigorously define the nigral pathology by process of elimination. However, as clinicians progressively identified PD symptoms unresponsive to the gold standard drug l-DOPA, definitions of PD symptoms were redefined. Non-motor symptoms prodromal to motor symptoms just as pre-clinical to clinical, and conjointly emerged the concept of nigral versus extranigral degeneration in PD. While nigrostriatal degeneration is responsible for the neurobiological substrates of extrapyramydal motor features, extranigral degeneration corroborates a vast majority of other changes in discrete central, peripheral, and enteric nervous system nuclei, which together account for global symptoms of the human disease. As an extranigral site, spinal cord degeneration has also been implicated in PD progression. Interconnected to the upper CNS structures with descending and ascending pathways, spinal neurons participate in movement and sensory circuits, controlling movement and reflexes. Several clinical and in vivo studies have demonstrated signs of parkinsonism-related degenerative processes in spinal cord, which led to recent consideration of spinal cord as an area of potential therapeutic target. In a nutshell, this review explores how the existing animal models can actually reflect the human disease in order to facilitate PD research. Evolution of extranigral degeneration studies has been succinctly revisited, followed by a survey on animal models in light of recent findings in clinical PD. Together, it may help to develop effective therapeutic strategies for PD.