Navigation Links
Necrostatin-1 counteracts aluminum's neurotoxic effects

Amsterdam, NL, August 2, 2013 Investigators have linked aluminum accumulation in the brain as a possible contributing factor to neurodegenerative disorders such as Alzheimer's disease. A new study published in Restorative Neurology and Neuroscience sheds light on the mechanism underlying aluminum-induced neuronal cell death and identifies necrostatin-1 as a substance which counteracts several of aluminum's neurotoxic effects.

Researchers have long focused on why neurons die in degenerative diseases. One process is apoptosis, a form of gene-directed programmed cell death which removes unnecessary, aged, or damaged cells. When neurons die as a result of stroke, trauma, or other insult, the process is known as necrosis. Recently, a new type of necrosis, necroptosis (programmed necrosis), has been implicated in the cell demise process. In this report, the results of several experiments support the hypothesis that aluminum-induced neuronal cell death is, to a large extent, due to necroptosis, says lead investigator Qinli Zhang, PhD, of the Department of Occupational Health, Ministry of Education Key Laboratory, School of Public Health of Shanxi Medical University in Taiyuan China.

For instance, when aluminum was added to mouse cortical neurons grown in cell culture, the cells began to die. By adding inhibitors of apoptosis (zVAD-fmk), of autophagy (3-methyladenin, 3-MA), or of necroptosis (necrostatin-1, Nec-1), investigators showed that all treatments enhanced cell viability although Nec-1 demonstrated the strongest protection. Using fluorescent microscopy, in which surviving neural cells stain green, apoptotic cells stain orange, and necrotic cells stain red, the investigators demonstrated Al-induced cell death as well as dose-dependent reduction of necroptosis with Nec-1.

When aluminum was injected into the cerebral ventricles of living mice, brain tissue analysis revealed shrunken and abnormal-looking neurons. When Nec-1 was injected simultaneously with aluminum into the ventricles, more surviving neurons could be seen, especially when higher doses of Nec-1 were used. When the investigators measured cell death-related proteins in the brain, a marker protein of necroptosis known as RIP1 showed the most changes, compared to marker proteins of apoptosis or autophagy. Similar findings were found for Alzheimer-related proteins: aluminum exposure increased the expression of mGluR2, mGluR5, Aβ, and Tau levels while Nec-1 treatment resulted in dose-dependent reductions of these protein levels.

Noting that "progressive cell loss in specific neuronal populations associated with typical learning and memory dysfunction is a pathological hallmark of neurodegenerative disorders, especially in AD," principal investigator Qiao Niu, MD, PhD, Director, Department of Occupational Health and Director, Institute of Preventive Medicine, Shanxi Medical University, and the team evaluated learning and memory in mice using the Morris Water Maze test. Al-treated mice performed poorly on the test and performance significantly improved if the mice were treated with Nec-1. Interestingly, if Nec-1 treatment was delayed for 2, 4, or 8 hours after the aluminum was introduced, Nec-1 had a protective effect less than simultaneous administration. Impaired cognitive performance was also correlated with reduced mGluR2 and mGluR5 protein in the cortex. "Nec-1, in addition to its use as a therapeutic agent for cell death, might therefore be of use in slowing the progression of the cognitive deficits associated with neuronal degeneration," says Dr. Niu.

The study demonstrates that Nec-1 may be useful for future prevention of and therapy for neurodegenerative disorders.


Contact: Daphne Watrin
IOS Press

Related medicine news :

1. Acai counteracts oxidative stress, lengthens lifespan in fruit flies
2. Young girls more likely to report side effects after HPV vaccine
3. Preteens More Likely to Report HPV Vaccine Side Effects
4. Breast cancer patients suffer treatment-related side effects long after completing care
5. Breast Cancer Treatment Side Effects May Last for Years
6. Baldness Drug May Cause Sexual Side Effects: FDA
7. Study examines adverse effects among different radiation therapies for prostate cancer
8. LA BioMeds Dr. John Tsuang examines effects of Ibudilast and metamphetamines
9. Moffitt researcher publishes book on nutritional management of cancer treatment effects
10. Researchers see BPA effects in monkey mammary glands
11. Many Primary Care Docs Dont Know Long-Term Effects of Chemo: Survey
Post Your Comments:
(Date:11/25/2015)... ... ... “While riding the bus, I saw a passenger in a wheelchair drenched from ... a convenient and comfortable way to protect them from bad weather, so I invented ... during cold or inclement weather. In doing so, it ensures that the user remains ...
(Date:11/25/2015)... , ... November 25, 2015 , ... ... (PHA) announces the nation’s Periwinkle Pioneers, individuals and groups responsible for advancing care ... disease. The Periwinkle Pioneers, nominated by the public, will receive special recognition throughout ...
(Date:11/25/2015)... ... November 25, 2015 , ... An unlikely combination ... in a way for homeless people to have a more dignified and comfortable ... initiative whereby they are repurposing plastic bags into sleeping mats for the homeless. ...
(Date:11/25/2015)... ... November 25, 2015 , ... ... focused on providing comprehensive solutions involving adult stem cell therapies to patients with ... deemed the “Regenestem” name as a Registered Trademark (RTM). , Organizations are required ...
(Date:11/24/2015)... ... 2015 , ... Genesis Chiropractic Software helps practice owners automate ... between the practice owner and the patient that automatically manages all five aspects ... Click here to learn more. , According to Dr. Brian ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... , November 25, 2015 Kitov ... ) (TASE: KTOV), a biopharmaceutical company focused on the ... various clinical conditions, today announced the closing of its ... Shares ( ADSs ), each representing 20 ordinary shares ... 3,158,900 ADSs. The ADSs and warrants were issued in ...
(Date:11/25/2015)... , Nov. 25, 2015 Allergan ... pharmaceutical company, and Rugen Therapeutics, a start-up  biotechnology ... for unmet CNS disorders and funded by the ... they have entered into an exclusive collaboration to ... for Autism Spectrum Disorders (ASD) and Obsessive Compulsive ...
(Date:11/25/2015)... Israel , November 25, 2015 ... "New Investors"), pursuant to which BioLight and the New ... IOPtima Ltd. subsidiary ("IOPtima") via a private placement. The ... of its innovative IOPtimate™ system used in the treatment ... approval pathway process for the IOPtimate™ system with the ...
Breaking Medicine Technology: