Autotoxicity, methylation and a road to the prevention of Parkinson’s disease

Williams, Adrian; Ramsden, D.

doi:10.1016/j.jocn.2004.10.002

Cited by 55 publications

(49 citation statements)

References 72 publications

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“…The accumulation of high concentration of intracellular NAM may thus impair functions of SIRT1 and other sirtuin enzymes, and preventing accumulation of intracellular NAM would be critical for maintaining active SIRT1 functions. NAM reduction can be achieved through NAM methylation by NAM Nmethyltransferase that targets it for excretion (Williams and Ramsden, 2005), or by recycling NAM back to NAD þ by the salvage pathway ( Figure 1a). We hypothesized that enzymes responsible for maintenance of cellular NAM level, NAM N-methyltransferase and rate-limiting NAD þ salvage pathway enzyme NAMPT, might also be upregulated in cancer cells in order to maintain active SIRT1 function.…”

Section: Nampt Is Overexpressed In Human Prostate Cancermentioning

confidence: 99%

NAMPT overexpression in prostate cancer and its contribution to tumor cell survival and stress response

et al. 2010

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Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in regenerating nicotinamide adenine dinucleotide (NAD þ ) from nicotinamide in mammals. NAMPT has crucial roles for many cellular functions by regulating NAD þ -dependent SIRT1 deacetylase. However, roles of NAMPT in cancer are poorly defined. In this study, we show that NAMPT is prominently overexpressed in human prostate cancer cells along with SIRT1. Elevation of NAMPT expression occurs early for the prostate neoplasia. Inhibition of NAMPT significantly suppresses cell growth in culture, soft agar colony formation, cell invasion and growth of xenografted prostate cancer cells in mice. NAMPT knockdown sensitizes prostate cancer cells to oxidative stress caused by H 2 O 2 or chemotherapeutic treatment. Overexpression of NAMPT increases prostate cancer cell resistance to oxidative stress, which is partially blocked by SIRT1 knockdown. We demonstrate that in addition to modulating SIRT1 functions, the NAMPT inhibition reduces forkhead box, class 'O' (FOXO)3a protein expression and its downstream anti-oxidant genes catalase and manganese superoxide dismutase. Our results suggest important roles of concomitant upregulation of NAMPT and SIRT1 along with increased FOXO3a protein level for prostate carcinogenesis and their contribution to oxidative stress resistance of prostate cancer cells. These findings may have implications for exploring the NAMPT pathway for prostate cancer prevention and treatment.

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Section: Nampt Is Overexpressed In Human Prostate Cancermentioning

confidence: 99%

NAMPT overexpression in prostate cancer and its contribution to tumor cell survival and stress response

et al. 2010

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“…Several N-methylated pyridines are well-established dopaminergic toxins and the NNMT can convert pyridines into toxic compounds (such as 4-phenylpyridine into N-methyl-4-phenylpyridinium ion [MPP + ]). NNMT has been shown to be present in the human brain, a necessity for neurotoxicity, because charged compounds cannot cross the blood-brain barrier (Williams & Ramsden, 2005). NNMT was one of the potential tumor biomarkers identified in a wide range of tumors such as thyroid, gastric, colorectal, renal, and lung cancer .…”

Section: N-methylationmentioning

confidence: 99%

Phase II Drug Metabolism

Jančová¹,

Siller²

2012

Topics on Drug Metabolism

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“…Más allá de lo que "se postula como probable etiología" (13) la EPI es casi con plena seguridad una autointoxicación (19). Se admite que la falla neuroquímica que determina los signos motores mas graves de la EPI es la bajísima producción de dopamina en el encéfalo y en particular las neuronas de la sustancia negra (SN) debida a la disminución extrema en la actividad de una ortofenolasa la tirosinhidroxilasa (TH) que forma levodopa a partir de la tirosina (20).…”

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Reflexiones sobre la Biosíntesis de la Morfina y el Parkinson Idiopático

Perea-Sasiaín¹

2007

Rev. salud pública

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RESUMENCon base en un caso personal estudiado en forma diaria y continua se deduce que la enfermedad de Parkinson idiopática es una autointoxicación endógena por alteraciones en la biosíntesis de la morfina, y se propone la determinación de los niveles de ésta en la sangre tanto en los parkinsonianos antes de cualquier tratamiento y, con el fin de establecer su diagnóstico preclínico, en los depresivos que constituyen el grupo mas afectado por la enfermedad de Parkinson.Palabras Clave: Biosíntesis, morfina, Parkinson, diagnóstico (fuente: DeCS, BIREME). ABSTRACTBased on a day-by-day, in-depth study of a clinical case, it was deduced that Parkinson's disease results in autointoxication, due to damage to morphine biosynthesis. Blood morphine levels should be studied in patients suffering from Parkinson's disease before treatment as well as in depressive patients (being the group most affected by Parkinson´s disease) to achieve early preclinical diagnosis.Key Words: Biosynthesis, morphine, Parkinson's disease, diagnosis (source: MeSH, NLM). traído y desecado de los frutos inmaduros de la adormidera, o en Colombia amapola, Papaver somniferum L (1). Solo otra especie en el reino vegetal produce morfina Papaver setigerum DC que unos consideran una sinonimia y otros que la primera son variedades de cultivo. Se debe destacar la habilidad del hombre l pasado año se cumplieron dos siglos de la primera publicación y este año ciento noventa de la última de Sertürner sobre la extracción, el aislamiento y la caracterización de la morfina a partir del opio, látex ex- E 308Rev. salud pública. 9 (2): 308-314. 2007 Ensayo/Essay

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Autotoxicity, methylation and a road to the prevention of Parkinson’s disease

Cited by 55 publications

References 72 publications

NAMPT overexpression in prostate cancer and its contribution to tumor cell survival and stress response

NAMPT overexpression in prostate cancer and its contribution to tumor cell survival and stress response

Phase II Drug Metabolism

Reflexiones sobre la Biosíntesis de la Morfina y el Parkinson Idiopático

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