کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5549082 1556600 2017 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
HIV-1 Vpr disrupts mitochondria axonal transport and accelerates neuronal aging
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
HIV-1 Vpr disrupts mitochondria axonal transport and accelerates neuronal aging
چکیده انگلیسی


- HIV-1 Vpr impaired mitochondria axonal transport.
- HIV-1 Vpr altered mitochondria axonal transport related to intracellular ATP reduction.
- Elevated α-synuclein level also contributed to the effect of Vpr.
- Low concentration of HIV-1 Vpr accelerated neuronal aging instead of causing cell death.

Disruption of mitochondria axonal transport, essential for the maintenance of synaptic and neuronal integrity and function, has been identified in neurodegenerative diseases. Whether HIV-1 viral proteins affect mitochondria axonal transport is unknown, albeit HIV-associated neurocognitive disorders occur in around half of the patients living with HIV. Therefore, we sought to examine the effect of HIV-1 viral protein R (Vpr) on mitochondria axonal transport. Using mice primary neuronal cultures, we demonstrated that 4-day Vpr treatment reduced the ratio of moving mitochondria associated with (i) less energy (ATP) supply, (ii) reduction in Miro-1 and (iii) increase of α-synuclein which led to loss of microtubule stability as demonstrated by inconsecutive distribution of acetylated α-tubulin along the axons. Interestingly, the effect of Vpr on mitochondria axonal transport was partially restored in the presence of bongkrekic acid, a compound that negatively affected the Vpr-adenine nucleotide translocator (ANT) interaction and totally restored the ATP level in neurons. This indicated Vpr impaired mitochondria axonal transport partially related to its interaction with ANT. The above effect of Vpr was similar to the data obtained from hippocampal tissues isolated from 18-month-old aging mice compared to 5-month-old mice. In accord with previous clinical findings that HIV infection prematurely ages the brain and increases the susceptibility to HAND, we found that Vpr induced aging markers in neurons. Thus, we concluded that instead of causing cell death, low concentration of HIV-1 Vpr altered neuronal function related with inhibition of mitochondria axonal transport which might contribute to the accelerated neuronal aging.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 117, 1 May 2017, Pages 364-375
نویسندگان
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