Abstract
Parkinson’s disease is mainly characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Together with the small number, the high vulnerability of the dopaminergic neurons is a major pathogenic culprit of Parkinson’s disease. Our previous findings of a higher survival of dopaminergic neurons in the substantia nigra co-expressing Nogo-A in an animal model of Parkinson’s disease suggested that Nogo-A may be associated with dopaminergic neurons resilience against Parkinson’s disease neurodegeneration. In the present study, we have addressed the expression of Nogo-A in the dopaminergic neurons in the substantia nigra in postmortem specimens of diseased and non-diseased subjects of different ages. For this purpose, in a collaborative effort we developed a tissue micro array (TMA) that allows for simultaneous staining of many samples in a single run. Interestingly, and in contrast to the observations gathered during normal aging and in the animal model of Parkinson’s disease, increasing age was significantly associated with a lower co-expression of Nogo-A in nigral dopaminergic neurons of patients with Parkinson’s disease. In sum, while Nogo-A expression in dopaminergic neurons is higher with increasing age, the opposite is the case in Parkinson’s disease. These observations suggest that Nogo-A might play a substantial role in the vulnerability of dopaminergic neurons in Parkinson’s disease.
Highlights
Parkinson’s Disease (PD) is the second most frequent neurodegenerative disorder, and among this category it is the fastest growing source of disability [1]
The primary trigger of the motor symptoms of PD consists in the depletion of dopamine in the striatum, resulting from a progressive loss of mesencephalic dopaminergic (DA) neurons projecting from the substantia nigra pars compacta (SNc)
A gradual and moderate decrease in DA neuron densities in the SNc appears to be a physiological process associated with aging, which seems to differ in some aspects to the neurodegenerative process occurring in PD [8,9,10,11]
Summary
Parkinson’s Disease (PD) is the second most frequent neurodegenerative disorder, and among this category it is the fastest growing source of disability [1]. A gradual and moderate decrease in DA neuron densities in the SNc appears to be a physiological process associated with aging, which seems to differ in some aspects to the neurodegenerative process occurring in PD [8,9,10,11]. These observations underscore the importance of a thorough comprehension of the determinants of DA neuron viability; a better characterization of DA neurons and in particular those spared during aging and in PD could help to unravel the mechanisms of neurodegeneration and identify new targets to modify its progression
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