As per a recent study conducted by a group of researchers in Amsterdam, Netherlands, state that, daeep brain stimulation of the subthalamic nucleus alleviates motor symptoms in Parkinson's disease patients. However, some patients suffer from cognitive and emotional changes.These side effects are most likely caused by current spread to the cognitive and limbic territories in the subthalamic nucleus. The aim of this study was to identify the motor part of the subthalamic nucleus to reduce stimulation-induced behavioral side effects, by using motor cortex stimulation. They describe the results of subthalamic nucleus neuronal responses to stimulation of the hand area of the motor cortex and evaluate the safety of this novel technique. Responses differed between regions within the subthalamic nucleus. In the anterior and lateral electrode at dorsal levels of the subthalamic nucleus, an early excitation (similar to 5-45 ms) and subsequent inhibition (45-105 ms) were seen. The lateral electrode also showed a late excitation (similar to 125-160 ms). Focal seizures were observed following motor cortex stimulation (Daniluk et al, 2010, 201).
Progressive accumulation of clumps of the protein alpha-synuclein in the brains of patients with Parkinson's disease coincides with the onset of motor dysfunction. However, whether these clumps are sufficient to trigger neurode-generation, and how these clumps spread throughout the brain, remained unclear. A group of colleagues in one of the study found that injecting preformed clumps of human alpha-synuclein into the brains of young mice accelerated disease onset and severity (Fernandez, 2010, pp: 557).
These clumps seemed to act as "seeds" that recruited even the mouse version of alpha-synuclein into new clumps, which then spread throughout the brain. The pattern of spreading from neuron to neuron suggests that the clumps may hijack the highway travelled by normal brain signals (Chwieduk, 2010, pp: 327).
Recent Findings on Parkinson's disease
These findings suggest that Parkinson's disease, like other neuro degenerative diseases including Alzheimer's, may start and progress due to abnormal aggregation and accumulation of proteins within the brain. What gets these clumps going in the first place remains unclear. Mitochondrial dysfunction represents a critical event in the pathogenesis of PD.
It was demonstrated that wild-type (WT) LRRK2 expression caused mitochondrial fragmentation along with increased mitochondrial dynamin-like protein (DLP1, also known as DRP1), a fission protein, which was further exacerbated by expression of PD-associated mutants (R1441C or G2019S) in both SH-SY5Y and differentiated primary cortical neurons. They also found that LRRK2 interacted with DLP1, and LRRK2DLP1 interaction was enhanced by PD-associated mutations that probably results in increased mitochondrial DLP1 levels. Co-expression of dominant-negative DLP1 K38A or WT Mfn2 blocked LRRK2-induced mitochondrial fragmentation, mitochondrial dysfunction and neuronal toxicity. Importantly, mitochondrial fragmentation and dysfunction were not observed in cells expressing either GTP-binding deficient mutant LRRK2 K1347A or kinase-dead mutant D1994A which has minimal interaction with DLP1 and did not increase the mitochondrial DLP1 level.
They concluded that LRRK2 regulates mitochondrial dynamics by increasing mitochondrial DLP1 through its direct interaction with DLP1, and LRRK2 kinase activity plays a critical role in this process. The Role of the Parkinson's Disease Gene PARK9 in Essential ...