Chronic Bacterial and Viral Infections in Neurodegenerative and Neurobehavioral Diseases

Garth L. Nicolson, PhD

Disclosures

Lab Med. 2008;39(5):291-299. 

In This Article

Parkinson's Disease

Parkinson's disease (PD) is characterized by akinesia, muscular rigidity, and resting tremor. Also present are autonomic dysfunction, olfactory disturbances, depression, sensory and sleep disturbances, and frequently dementia.[102] Parkinson's disease pathology indicates a progressive loss of the dopamine neurons of the substantia nigra together with the presence of Lewy bodies and alpha-synuclein. More extensive brain degeneration also occurs, from the medulla oblongata to the cerebral cortex.[103,104]

Although there is consensus among investigators that age-related inclusion bodies and protein aggregations or defects in their degradation occur in PD, their cause and role in PD pathogenesis remains a subject of intense research.[103,104] Some evidence suggests a relationship between PD and specific genetic changes, such as changes in the genes affecting mitochondria, protein degradation, organelle trafficking, and vesicular fusion, and in proteins involved in oxidative stress or antioxidant function.[102] Inflammation has also been associated with PD pathology.[105]

Similar to other neurodegenerative diseases, the pathogenesis of PD has been proposed to be due to multiple genetic and neurotoxic hits that produce oxidative damage and cell death; however, in the case of PD the relevant targets of toxic events are neuromelanin-containing dopaminergic neurons of the substantia nigra.[104,106] A case-control study in Italy indicated that multiple environmental factors and genetic background were statistically related risk factors for PD.[107] Among these, toxic exposures (over many years) and trauma early in life may be important in the pathogenesis of PD.[108] For example, early life exposure to brain injury, chemicals, or infections may initiate a cyclic inflammatory process involving oxidative damage, excitotoxicity, mitochondrial dysfunction, and altered proteolysis that later in life results in substantia nigra neuron death by apoptosis.[109,110,111]

The possible role of chronic infections in PD pathogenesis has been proposed for a number of years.[109] One infection found in PD that has aroused considerable interest is the presence of chronic gastrointestinal Helicobacter pylori, as treatment of this infection offered some relief to late stage cachexia in PD patients who were receiving L-dopa.[112] Indeed, Pierantozzi and colleagues[113] found that Helicobacter pylori-infected PD patients had reduced L-dopa absorption and increased clinical disability, while treating this infection increased L-dopa absorption and reduced clinical disability.[114]Helicobacter pylori may not be directly involved in PD, but its systemic presence could affect the progression and treatment of PD, probably by stimulating inflammation and autoimmunity.[115]

Inflammation and autoimmune responses have also been attributed to other chronic infections found in PD.[115,116,117] Indeed, experimental models of PD have been developed using neurological, viral, or bacterial infections to initiate the pathogenic process.[118,119] In humans, spirochetes have been found in Lewy bodies of PD patients.[29] Other infections, such as viral encephalitis,[120] AIDS-associated opportunistic infections of the basal ganglia,[121] coronavirus,[122] and other infections,[63,123,124] have been found in PD and could be important in stimulating inflammation and autoimmune responses. Richy and Mégraud[125] have stressed, however, that more rigorous investigations will be required to establish whether a causal link exists between infections and PD.

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