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The progression of Parkinson disease: a hypothesis


, : The progression of Parkinson disease: a hypothesis. Neurology 68(12): 948-952

Recent neuropathologic studies suggest that Parkinson disease (PD) does not begin in the substantia nigra compacta (SNc) but only involves this region later in the course of the disease. It is proposed that once the SNc is affected by the original pathobiological process (for example, protein aggregation), additional processes more specific to dopaminergic neurons are triggered (including sources of oxidative stress such as increased dopamine turnover, reduced levels of reduced glutathione, increased iron, and the presence of neuromelanin, as well as altered calcium homeostasis and excitotoxicity). This results in an acceleration of cell loss in the SNc, causing nigrostriatal degeneration to both reach a threshold for symptoms in advance of earlier affected brain areas and progress more rapidly than other aspects of the disease. Neuroprotective therapy directed solely at more general biologic processes may not have sufficient effects on this accelerated degeneration in the SNc, while neuroprotective therapy designed exclusively to slow the progression of dopaminergic cell loss will not alter the progression of the nondopaminergic symptoms that contribute the greatest disability in the later stages of the disease. Effective disease-modifying therapy may require a cocktail combining treatments designed to address the basic mechanisms of the neurodegeneration and the additional biologic processes specific to the dopaminergic SNc. This hypothesis has implications for the development of disease-modifying therapy and the interpretation of endpoints of clinical trials evaluating the efficacy of such treatments.

US$19.90

PMID: 17372132

DOI: 10.1212/01.wnl.0000257110.91041.5d


Other references

Pello, M.J.; Beauregard, W.; Shaikh, K.; Camishion, R.C., 1984: Colon operations without wound infection. Principles and techniques in 101 cases. A total of 101 consecutive elective colon operations were performed with no postoperative wound infection. Patients with a wide variety of diagnoses and procedures were included in the series. Many factors contribute to the formation of postoperat...

Charpentier, B.; François, Hélène.; Beaudreuil, Séverine.; Dürrbach, A., 2015: Necessary but sometimes complicated coordination of healthcare procedures. The example of chronic renal failure. Chronic renalfailure (CRF), one of several disorders involving progressive loss of function of a vital organ, is a paradigm for medical/paramedical coordination networks, especially in view of the explosion of the geriatric CRF/dialysis population...

Saghbini, M.G.; Wing, L.R.; Hamlin, S., 2003: A modified Ames assay for mutagenicity screening. Environmental & Molecular Mutagenesis 41(3): 202

Reali, D.; Caroli, G.; Filippi, S.; Simonetti, S., 1977: Presence and etio-epidemiological significance of halophilic vibriones in various material. In this work data of isolation of halophilic vibrios from coastal water of central Tyrrhenian sea are reported, and the epidemiological significance of such strains is discussed. V. Parahaemolyticus was identified in 8 out of 20 samples of sea wat...

Fujita, K., 1968: Study of the purification of a toxic factor in the urine of schizophrenic subjects. Sapporo Igaku Zasshi. Sapporo Medical Journal 33(1): 12-21

Shnitko, T.A.; Robinson, D.L., 2015: Regional variation in phasic dopamine release during alcohol and sucrose self-administration in rats. While dopamine input to the dorsal striatum is well-known to be critical for action selection, including alcohol-motivated behaviors, it is unknown whether changes in phasic dopamine accompany these behaviors. Long-term alcohol abuse is believed t...

Skjelhaugen, O.J.; Fjelldal, E., 1993: Methods for collecting and storing of urine: under intensive farming conditions. A collecting system for cattle or pig urine must drain out the pure urine as soon as possible after production to avoid mixing with faeces and litter. Three systems are described, all based on drainage by gravity. None of the systems are recommend...

Cheung, C.K.Y.; Wu, J.C.Y., 2015: Genetic polymorphism in pathogenesis of irritable bowel syndrome. Irritable bowel syndrome (IBS) is a complex symptom-based disorder without established biomarkers or putative pathophysiology. IBS is a common functional gastrointestinal disorder which is defined as recurrent abdominal pain or discomfort that has...

Yu, M.; Xue, T.; Chen, T.; Fang, J.; Pan, Q.; Deng, Y.; Li, L.; Chen, K.; Wang, Y., 2017: Maternal inheritance of Nanog ortholog in blunt-snout bream. The homeodomain transcription factor Nanog plays an essential role in maintaining pluripotency and self-renewal of embryonic stem cells in mammals. However, the evolutionary conservation of its ortholog in teleosts remains elusive. Here we isolate...

Steffan, S.A., 1997: Flower-visitors of Baccharis pilularis De Candolle subsp. consanguinea (De Candolle) C. B. Wolf (Asteraceae) in Berkeley, California. Representatives of at least 55 insect species (in 5 orders and 32 families) were collected from flowers of Baccharis pilularis subsp. consanguinea in Berkeley, California, in October 1992.