Navigation Links
Necrostatin-1 counteracts aluminum's neurotoxic effects
Date:8/5/2013

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
d.watrin@iospress.nl
31-206-883-355
IOS Press
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... June 27, 2016 , ... ... technology to revolutionize the emergency ambulance transport experience for the millions of people ... how Uber has disrupted the taxi industry through the use of technology. Now, ...
(Date:6/26/2016)... ... , ... On June 10-11, 2016, A Forever Recovery, a holistic treatment center ... Breakfast Table in Battle Creek, MI, where the rehabilitation facility is located. This annual ... the world’s leading providers of cereal and other breakfast foods. Its residents often refer ...
(Date:6/26/2016)... NC (PRWEB) , ... June 26, 2016 , ... Brent Kasmer, a legally blind and ... to be personalized through a fitness app. The fitness app plans to fix the two ... currently only offer a one size fits all type program , They don’t ...
(Date:6/25/2016)... ... 2016 , ... Austin residents seeking Mohs surgery services, can now turn to ... Dr. Russell Peckham for medical and surgical dermatology. , Dr. Dorsey brings specialization to ... fellowship in Mohs Micrographic Surgery completed by Dr. Dorsey was under the direction of ...
(Date:6/25/2016)... ... June 25, 2016 , ... First Choice Emergency Room , the largest ... as the Medical Director of its new Mesquite-Samuell Farm facility. , “We are ... Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical Director of First Choice Emergency ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... Colombia , June 23, 2016  Astellas today announced the establishment of Astellas Farma Colombia (AFC), a new ... affiliate in Latin America . ... ... ... ...
(Date:6/23/2016)... Pa. , June 23, 2016 The ... in an outpatient dialysis facility.  Treatments are usually 3 ... 6 hours per visit, including travel time, equipment preparation ... a patient, but especially grueling for patients who are ... of a skilled nursing and rehabilitation centers for some ...
(Date:6/23/2016)... NEW YORK , June 23, 2016 ... rough waters, but it continues to present great opportunities ... featured companies for today: Intrexon Corp. (NYSE: ... ), Arena Pharmaceuticals Inc. (NASDAQ: ARNA ), ... Learn more about these stocks and receive your complimentary ...
Breaking Medicine Technology: