The cells of the body, brain cells included, are in a constantly shifting balance. Old and damaged cells undergo a form of programmed cell death known as apoptosis. While it sounds ominous, apoptosis is necessary to maintain the balance between new cell growth and cell death. Shifting the balance toward uncontrolled cell growth can result in cancer. However, when the balance shifts the other way and too many cells are destroyed, diseases can also arise. In the brain, this excess destruction of cells can lead to dementia.
Researchers at Georgetown University Medical Center discovered that HIV does not directly infect nerve cells, but instead blocks the formation of a growth factor known as mature BDNF (brain derived neurotrophic factor). When the level of this protein decreases in the brain, brain cells are unable to create the long dendritic and axonal branches required to communicate with each other, and die.
The researchers also uncovered the underlying mechanism for this premature cell death. Brain cells release a precursor to the BDNF growth factor called pro BDNF. This must be divided by enzymes in the brain to release the active BDNF form, which nourishes brain cells and maintains the connections between them. HIV blocks this division, resulting in high circulating levels of pro BDNF. Pro BDNF binds to a receptor on brain cells that contains a ‘death domain’, triggering apoptosis (cell death).
This HIV-induced imbalance between toxic pro BDNF and the healthy form of mature BDNF is similar to the imbalance seen in the aging brain. In a news release from Georgetown University, lead investigator Italo Mocchetti stated ‘“We believe we have discovered a general mechanism of neuronal decline that even explains what happens in some elderly folks. The HIV-infected patients who develop this syndrome are usually quite young, but their brains act old.” Lack of mature BDNF may also play a role in other chronic neurological conditions, including Parkinson’s and Huntington’s Diseases.
The hope is that this new research may eventually lead to the development of drugs effective in multiple forms of dementia. Blocking the receptor for pro BDNF could stop the deadly cascade leading to premature cell death, and slow the relentless pace of dementia in both patients with HIV and the elderly.(Online News pk)
