N-Acetyl Cysteine and Parkinsons

Acetylcysteine serves as a prodrug to L-cysteine.

L-cysteine is a precursor to the biologic antioxidant glutathione. Hence administration of acetylcysteine replenishes glutathione stores.[60]

– Glutathione, along with oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO), have been found to bind to the glutamate recognition site of the NMDA and AMPA receptors (via their γ-glutamyl moieties), and may be endogenous neuromodulators.[61][62] At millimolar concentrations, they may also modulate the redox state of the NMDA receptor complex.[62] In addition, glutathione has been found to bind to and activate ionotropic receptors that are different from any other excitatory amino acid receptor, and which may constitute glutathione receptors, potentially making it a neurotransmitter.[63] As such, since N-acetylcysteine is a prodrug of glutathione, it may modulate all of the aforementioned receptors as well.

– Glutathione also modulates the NMDA receptor by acting at the redox site.[33][64]

L-cysteine also serves as a precursor to cystine which in turn serves as a substrate for the cystine-glutamate antiporter on astrocytes hence increasing glutamate release into the extracellular space. This glutamate in turn acts on mGluR2/3 receptors, and at higher doses of acetylcysteine, mGluR5.[65][66]

Acetylcysteine also possesses some anti-inflammatory effects possibly via inhibiting NF-κB and modulating cytokine synthesis.[33]

Pharmacokinetics

Extensively liver metabolized; CYP450 minimal. Urine excretion 22-30% with a half-life of 5.6 hours in adults and 11 hours in neonates.

Chemistry

Acetylcysteine is the Nacetyl derivative of the amino acid L-cysteine, and is a precursor in the formation of the antioxidant glutathione in the body. The thiol (sulfhydryl) group confers antioxidant effects and is able to reduce free radicals.

 


Do you have Parkinson’s disease?

The National Institutes of Health (NIH) in Bethesda, Maryland seeks volunteers with Parkinson’s disease to be part of a clinical research study about whether N-acetylcysteine (NAC) has a particular effect on brain chemistry in patients with Parkinson’s disease. Researchers are evaluating whether NAC can protect the nerve cells in the brain that control movement.

You may qualify if you:

  • Are at least 18 years old
  • Have been diagnosed with Parkinson’s disease within the past 5 years
  • Are taking a type of drug called an MAO inhibitor (e.g. Azilect, Eldepryl)
  • Are able to provide your own consent

You may not qualify if you:

  • Are taking levodopa in any form
  • Are unable to travel safely to the NIH Clinical Center in Bethesda, Maryland
  • Know you have an allergy to NAC
  • Are pregnant or breast feeding

Study information:

  • To determine if you are eligible for the study, you will have a screening visit that will include a review of your medical history, a physical examination, and blood tests.
  • If you are found to be eligible, you will have a 4-8 day inpatient stay.
  • During your stay you will take NAC by mouth for about 2 days.
  • Before and after taking NAC, you will have a lumbar puncture (spinal tap).
  • Compensation will be provided.

Study Location: The NIH Clinical Center is America’s research hospital and is located in Bethesda, Maryland, on the Metro red line (Medical Center stop).

To learn about participating, call:
Office of Patient Recruitment
1-866-444-1132
TTY: 1-866-411-1010
Online: URL: https://go.usa.gov/xXSsQ
NIH study #17-N-0076


Food sources of NAC : Fish, eggs, legumes, seeds and nuts , whole grains

 


Research

  • It is being studied in conditions, such as autism, where cysteine and related sulfur amino acids may be depleted due to multifactorial dysfunction of methylation pathways involved in methionine catabolism.[69]
  • Acetylcysteine in a double-blind placebo-controlled trial appears to reduce the effects of blast induced mild traumatic brain and neurological injury in soldiers.[70]Animal studies have also demonstrated its efficacy in reducing the damage associated with moderate traumatic brain or spinal injury, and also ischemia-induced brain injury. In particular, it has been demonstrated to reduce neuronal losses and to improve cognitive and neurological outcomes associated with these traumatic events.[34]
  • It has been suggested that acetylcysteine may help people with Samter’s triad by increasing levels of glutathione allowing faster breakdown of salicylates, though there is no evidence that it is of benefit.[71]
  • It has been shown to help women with PCOS (polycystic ovary syndrome) to reduce insulin problems and possibly improve fertility.[72]
  • Small studies have shown acetylcysteine to be of benefit to people with blepharitis.[73] and has been shown to reduce ocular soreness caused by Sjögren’s syndrome.[74]
  • It has been shown effective in the treatment of Unverricht-Lundborg disease in an open trial in 4 patients. A marked decrease in myoclonus and some normalization of somatosensory evoked potentials with acetylcysteine treatment has been documented.[75][76]
  • The effect of acetylcysteine in combination with glucocorticoids (combination group) for people who have severe alcoholic hepatitis was examined and showed that the combination of acetylcysteine with prednisolone decreased mortality significantly at one month compared to the prednisolone-only group (8% vs 24%, P=0.006). However, the improvement was not as significant at 3 months or 6 months (22% vs 34%, P=0.06) and (27% vs 38%, P=0.07). Factors that were associated with increased 6-month survival included younger age, shorter prothrombin time, lower levels of bilirubin in baseline studies, and decrease in bilirubin on day 14, all (P<0.001). Death due to hepatorenal syndrome occurred less frequently for the combination group at 6 months (9% vs 22%, P=0.02) and infections were also less frequent in the combination group as well (P=0.001). Six-month survival, the primary outcome, was not improved in conclusion.[77]
  • Acetylcysteine has been hypothesized to be beneficial in Parkinson’s disease. It is currently undergoing clinical trials.[78][79][80]
  • Addiction to certain addictive drugs (e.g., cocaine, heroin, alcohol, and nicotine) is correlated with a persistent reduction in the expression of excitatory amino acid transporter 2 (EAAT2) in the nucleus accumbens (NAcc);[40] the reduced expression of EAAT2 in this region is implicated in addictive drug-seeking behavior.[40] In particular, the long-term dysregulation of glutamate neurotransmission in the NAcc of addicts is associated with an increase in vulnerability to relapse after re-exposure to the addictive drug or its associated drug cues.[40] Drugs which help to normalize the expression of EAAT2 in this region, such as N-acetylcysteine, have been proposed as an adjunct therapy for the treatment of addiction to cocaine, nicotine, alcohol, and other drugs.[40

Author: connie dello buono

Health educator, author and enterpreneur motherhealth@gmail.com or conniedbuono@gmail.com ; cell 408-854-1883 Helping families in the bay area by providing compassionate and live-in caregivers for homebound bay area seniors. Blogs at www.clubalthea.com Developing a new site, www.avatarcare.net , for early cancer detection using genetics tests, telemedicine with electronic appointment scheduling with doctors, video chat with doctors, matching care providers with health consumers and a health concierge for all to reduce chronic care cost, find cancer cure and coordinate health care using predictive medicine and participatory.

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