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New Therapeutic Target for Parkinson’s Disease Investigated By Scientists At The University Of Houston

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New Therapeutic Target for Parkinson’s Disease Investigated By Scientists At The University Of Houston

Researchers at the University of Houston (UH) have discovered a new therapeutic target against Parkinson’s disease. They are optimistic that with this new therapeutic target, a nuclear receptor called liver X receptor beta (LXRbeta), Parkinson’s disease can not only be prevented but also treated. The study was conducted by researchers from the UH, Center for Nuclear Receptors and Cell Signaling (CNRCS), and published in the Proceedings of the National Academy of Sciences (PNAS).

Parkinson’s disease is a neurological disease that occurs due to insufficient production of dopamine in the brain. The disease is manifested by generalized skeletal muscle hypertonia and hypokinesia. Therefore, symptoms such as stiffness and fine tremor of the extremities appear. In more advanced stages, there are also symptoms regarding cognitive impairment: behavioral disturbances, sensory impairment, dementia. The most striking symptoms in Parkinson’s disease are related to movement. Patients with Parkinson’s disease have a specific walking with the trunk flexed forward and postural instability. Fine tremor of the extremities is also a characteristic symptom. Other signs and symptoms that occur are speech and swallowing impairments, voice changes and others.

Parkinson’s disease is a disease that affects mainly elderly and it is believed that it develops due to dopaminergic neuronal loss in the brain. These dopaminergic neurons play a role in controlling body motility and movement. This hypothesis is confirmed by the fact that blocking dopamine neurons in the brain by certain drugs (neuroleptics) cause a parkinsonian syndrome, similar to Parkinson’s disease.

Parkinson’s disease treatment aims to increase dopaminergic activity in the brain. Therefore, there are used drugs that either increase synaptic dopamine release or inhibit its degradation (selegiline). Another useful drug in Parkinson’s disease treatment is levodopa, which acts as a dopamine precursor. Other useful drugs are dopamine receptor agonist, such as bromocriptine, which allow lower levodopa doses.

Parkinson's Disease

Parkinson’s Disease

Researchers at the University of Houston (UH) have discovered that the nuclear receptor, liver X receptor beta (LXRbeta), which is found in microglia, plays an important role in the survival of dopaminergic neurons. This receptor has been discovered in 1995 and latest experiments showed that this receptor continue to show promise as a potential therapeutic target for this disease, as well as other neurological disorders..

To understand the relationship between LXRbeta and Parkinson’s disease, researchers used a very potent neurotoxin, called MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridina). MPTP is a compound found in street drugs, and it was observed that cause Parkinson’s disease in people who consumed this drugs. In their study, researchers used  MPTP in murine models to simulate the disease and to study its pathology and possible treatments.

The results showed that MPTP had a far more damaging effect on neurons in the absence LXRbeta. Additionally, scientists found that administrating a drug that activates LXRbeta receptors, they can prevented the destructive effects of MPTP and, therefore, may offer protection against midbrain neurodegeneration.

LXRbeta is not expressed in the dopamine-producing neurons, but instead in the microglia surrounding the neurons. Microglia are the police of the brain, keeping things in order. In Parkinson's disease the microglia are overactive and begin to destroy the healthy neurons in the neighborhood of those neurons damaged by MPTP. LXRbeta calms down the microglia and prevents collateral damage. Thus, we have discovered a novel therapeutic target for treatment of Parkinson's disease., Gustafsson, CNRCS director and professor whose lab discovered LXRbeta in 1995, said.