Recent Parkinson's Disease Research Articles

Parkinson’s Disease Identification using Deep Neural Network with RESNET50

Recent Parkinson's disease (PD) research has focused on recognizing vocal defects from people's prolonged vowel phonations or running speech since 90% of Parkinson's patients demonstrate vocal dysfunction in the early stages of the illness. This research provides a hybrid analysis of time and frequency and deep learning techniques for PD signal categorization based on ResNet50. The recommended strategy eliminates manual procedures to perform feature extraction in machine learning. 2D time-frequency graphs give frequency and energy information while retaining PD morphology. The method transforms 1D PD recordings into 2D time-frequency diagrams using hybrid HT/Wigner-Ville distribution (WVD). We obtained 91.04% accuracy in five-fold cross-validation and 86.86% in testing using RESNET50. F1-score achieved 0.89186. The suggested approach is more accurate than state-of-the-art models.

Functional Interactions of Disease‐Linked Disordered Proteins: Alpha‐Synuclein, Tau and Complexin

The proteins alpha‐synuclein and tau are linked to Parkinson's and Alzheimer's disease, respectively, yet little is known about their normal physiological functions, while complexin, a protein more loosely linked to neurological and psychiatric disorders, has several opposing functions whose mechanisms remain poorly understood. All three proteins are completely or highly disordered when free in solution. Structural characterization of different states of alpha‐synuclein has lead us to propose a model in which the protein can bridge between the synaptic vesicle and plasma membranes. This model also has implications for membrane‐induced synuclein aggregation. These topics will be discussed in the context of one of the most recent Parkinson's disease associated synuclein mutations. Tau is normally a microtubule binding protein, but can also bind to membrane surfaces, an interaction that may be either physiologically or pathologically relevant. Recent work in the lab has confirmed that tau‐membrane interactions are mediated by short amphipathic helices, which may also play a role in mediating membrane‐ or microtubule‐induced aggregation. Complexin contains a central helix motif that binds to assembled SNARE complexes, and this interaction is key to two opposing functions, enhancing synchronous exocytosis and inhibiting spontaneous vesicle fusion. Binding of the disordered C‐terminal domain of complexin to membranes is critical for its inhibitory function. We have shown that such binding is highly dependent on membrane curvature, and that a local structural transition to a helical conformation, again necessary for function, only occurs upon binding to highly curved membranes such as synaptic vesicles. Thus complexin's function is regulated by a membrane curvature dependent structural transition.

Eryptosis as a marker of Parkinson's disease.

A major trend in recent Parkinson's disease (PD) research is the investigation of biological markers that could help in identifying at-risk individuals or to track disease progression and response to therapies. Central to this is the knowledge that inflammation is a known hallmark of PD and of many other degenerative diseases. In the current work, we focus on inflammatory signalling in PD, using a systems approach that allows us to look at the disease in a more holistic way. We discuss cyclooxygenases, prostaglandins, thromboxanes and also iron in PD. These particular signalling molecules are involved in PD pathophysiology, but are also very important in an aberrant coagulation/hematology system. We present and discuss a hypothesis regarding the possible interaction of these aberrant signalling molecules implicated in PD, and suggest that these molecules may affect the erythrocytes of PD patients. This would be observable as changes in the morphology of the RBCs and of PD patients relative to healthy controls. We then show that the RBCs of PD patients are indeed rather dramatically deranged in their morphology, exhibiting eryptosis (a kind of programmed cell death). This morphological indicator may have useful diagnostic and prognostic significance.

α-Synuclein Expression Modulates Microglial Activation Phenotype

Recent Parkinson's disease research has focused on understanding the function of the cytosolic protein, alpha-synuclein, and its contribution to disease mechanisms. Within neurons, alpha-synuclein is hypothesized to have a role in regulating synaptic plasticity, vesicle release, and trafficking. In contrast, glial-expressed alpha-synuclein remains poorly described. Here, we examine the consequence of a loss of alpha-synuclein expression on microglial activation. Using a postnatal brain-derived culture system, we defined the phenotype of microglia from wild-type and knock-out alpha-synuclein mice (Scna-/-). Scna-/- microglia displayed a basally increased reactive phenotype compared with the wild-type cells and an exacerbated reactive phenotype after stimulation. They also exhibited dramatic morphologic differences compared with wild-type, presenting as large, ramified cells filled with vacuole-like structures. This corresponded with increased protein levels of activation markers, CD68 and beta1 integrin, in the Scna-/- cells. More importantly, Scna-/- microglia, after stimulation, secreted elevated levels of proinflammatory cytokines, TNFalpha (tumor necrosis factor alpha) and IL-6 (interleukin-6), compared with wild type. However, despite the reactive phenotype, Scna-/- cells had impaired phagocytic ability. We demonstrate for the first time that alpha-synuclein plays a critical role in modulating microglial activation state. We suggest that altered microglial alpha-synuclein expression will affect their phenotype as has already been demonstrated in neurons. This has direct ramifications for the contribution of microglia to the pathophysiology of disease, particularly in familial cases linked to altered alpha-synuclein expression.