Dr. Mohamed Salama
Head of Experimental Neurology Unit
MERC, Mansoura University,
Egypt

In rural living, individuals are exposed to variable environmental natural compound that have the ability to induce dopaminergic neuronal damage. Various epidemiological data suggested the potential role of these natural compounds to induce Parkinsonism (Caldwell et al., 2009). Epidemiological studies suggest that the prevalence of Parkinsonism is not affected by the industrial revolution. Moreover, it seems that pesticides exposure is not linked with PD prevalence. A finding that is supported by the failure of most of the synthetic toxins induced PD models to recapitulate the exact pathological features of the disease (Trimmer and Bennett, 2009). So, a new direction of using “natural” toxins in the modeling of Parkinsonism seems attractive. The success of these toxins to induce dopaminergic neuron death and protein aggregation in vitro led us to think of them as new candidates that could be able to improve animal models of Parkinsonism (Shen et al., 2010).

Inhibition of complex I of the mitochondrial respiratory chain has also been implicated in the pathophysiology of PD (Schapira et al., 1990). Many toxins of herbal, microbial or synthetic origin can induce neuronal cell death in cultured neurons in vitro (Höllerhage et al., 2009). The success of new environmental toxins to develop mitochondrial complex I inhibition and degeneration of dopaminergic neurons in vitro (Arif and Khan, 2010), coupled with epidemiological data suggesting natural environmental toxin involvement in Parkinsonism pathogenesis would invite us to think of these natural toxins as new candidates for developing models (Tanner, 2010).

The choice of certain natural toxins for PD modeling needs some guidelines as supposed by Shaw and Hoeglinger [2008].

1. The agent must be of natural origin.
2. The agent must be available worldwide to contribute to the wide prevalence of PD in
the whole world.
3. The agent must recapitulate PD pathology in experimental animals.

We are trying to explore the role of various natural agents, able to inhibit complex I, in developing PD in animals. This work is carried in Experimental Neurology Unit, MERC, Mansoura University. Defining possible agents can help in many aspects; first we will be able to develop invivo model that can recapitulate the pathological findings in PD. Moreover, we will be able to identify high risk population exposed to these factors.

References:

Caldwell KA, Tucci ML, Armagost J, Hodges TW, Chen J, et al. 2009 Investigating Bacterial Sources of Toxicity as an Environmental Contributor to Dopaminergic Neurodegeneration. PLoS ONE 4(10): e7227. doi:10.1371

Trimmer B. Bennett J. 2009 The cybrid model of sporadic Parkinson’s disease. Experimental Neurology 218: 320–325.

Shen W, McDowell K, Siebert A, Clark S, Dugger N, Valentino K, Jinnah H, Sztalryd C, Fishman P, Shaw C, Jafri S. Yarowsky P 2010 Environmental neurotoxin-induced progressive model of Parkinsonism in rats. Ann Neurol 68:70-80.
Schapira AH, Mann VM, Cooper JM, Dexter D, Daniel SE, Jenner P, Clark JB, Marsden CD. 1990 Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson’s disease. J Neurochem. 55(6):2142-2145.

Höllerhage M, Matusch A, Champy P, Lombès A, Ruberg M, Oertel WH, Höglinger GU. 2009 Natural lipophilic inhibitors of mitochondrial complex I are candidate toxins for sporadic neurodegenerative tau pathologies Experimental Neurology 220: 133–142.

Arif I. Khan H. 2010 Environmental toxins and Parkinson’s disease: Putative roles of impaired electron transport chain and oxidative stress. Toxicology and Industrial Health 26(2) 121–128.

Tanner C. 2010 Advances in Environmental Epidemiology. Movement Disorders 25: S58–S62.

Shaw C. Hoglinger G. 2008 Neurodegenerative Diseases: Neurotoxins as Sufficient Etiologic Agents? Neuromolecular Med. 2008 ; 10(1): 1-13.