Cerebrospinal fluid protein biomarkers in Parkinson's disease.

Proteomic profiling is an effective way to identify biomarkers for Parkinson's disease (PD). Cerebrospinal fluid (CSF) has direct connectivity with the brain and could be a source of finding biomarkers and their clinical implications. Comparative proteomic profiling has shown that a group of differentially displayed proteins exist. The studies performed using conventional and classical tools also supported the occurrence of these proteins. Many studies have highlighted the potential of CSF proteomic profiling for biomarker identification and their clinical applications. Some of these proteins are useful for disease diagnosis and prediction. Proteomic profiling of CSF also has immense potential to distinguish PD from similar neurodegenerative disorders. A few protein biomarkers help in fundamental knowledge generation and clinical interpretation. However, the specific biomarker of PD is not yet known. The use of proteomic approaches in clinical settings is also rare. A large-scale, multi-centric, multi-population and multi-continental study using multiple proteomic tools is warranted. Such a study can provide valuable, comprehensive and reliable information for a better understanding of PD and the development of specific biomarkers. The current article sheds light on the role of CSF proteomic profiling in identifying biomarkers of PD and their clinical implications. The article also explains the achievements, obstacles and hopes for future directions of this approach.

Is Gut Dysbiosis an Epicenter of Parkinson's Disease?

Once recognized as one of the most esoteric diseases of the central nervous system, Parkinson's disease (PD) is now deemed to be a chronic illness contributed by the central, autonomic and enteric nervous systems. Most likely, an accumulation of α-synuclein in the central and enteric nervous systems is the key that supports this viewpoint. Constipation, one of the non-motor hallmarks in roughly two-third of PD patients, is regulated by the composition of gut bacteria, which is assumed to set off the enteric α-synuclein accrual. Vagus nerve is suggested to direct the signal for α-synuclein over-expression and accumulation to the brain. While trillions of microorganisms reside in the intestinal tract, only one third of the proportion inhabits evenly in all individuals. Existence of an impaired gut-microbe-brain axis consonant with dysbiosis could be an epicenter of this inexplicable disorder. Any alteration in the structure and function of the gastrointestinal tract owing to exposure of endogenous or exogenous chemicals or toxicants could lead to dysbiosis. However, inconsistency in the symptoms even after exposure to same chemical or toxicant in PD patients emphatically creates a conundrum. While the level of a few specific neurotransmitters and metabolites is influenced by microbes, implication of dysbiosis is still debatable. Nevertheless, the scientific literature is overflowing with the remarkable observations supporting the role of dysbiosis in PD. Lack of specificity to differentially diagnose PD with non-PD or PD-plus syndrome, to identify highly precise drug targets and to develop therapeutic stratagems to encounter the disease on the basis of this approach, causes us to be open-minded about the dysbiosis theory. The article reviews the facts supporting gut dysbiosis as the foremost trigger for PD onset along with disagreements.

Unequivocal Biomarker for Parkinson's Disease: A Hunt that Remains a Pester.

Devastating motor features, lack of early prognostic tools, and absence of undeviating therapies call for an endeavor to develop biomarkers for Parkinson's disease (PD). A biomarker is anticipated to help in timely and selective diagnosis as well as to hunt for an appropriate treatment option. Peripheral fingerprints can be used to assess the progression, distinguish PD from other related disorders, and monitor the efficacy of therapeutic options. From the last two decades, peripheral blood is constantly targeted in search of an appropriate marker owing to minimal invasive procedure for collection, highly dynamic nature, and insignificant ethical concern. Besides, cerebrospinal fluid (CSF) is also preferred because of its close proximity to the brain. Employing conventional and contemporary sophisticated devices, a number of protein and non-protein entities, mainly metallic elements, have been shown to hold adequate potential to be used as biomarkers for monitoring progression and assessing treatment options for such a distressing neurodegenerative disorder. Classical strategies and relatively newer sophisticated tools, such as proteomics, deciphered the presence of an altered level of highly specific blood- and CSF-specific proteins, free metals, metal-binding proteins, common inflammatory proteins, and overexpressed/modified α-synuclein in PD patients. While several chemical entities are shown to be associated, not even a single protein or metal is converted into unambiguous disease fingerprint. The article provides an update on proteins and metals that are shown to possess enormous potential in the course of biomarker exploration but are unable to deliver a reliable indicator. The review also sheds light on the reasons of ineffective hit to hunt for an authentic fingerprint and proposes the doable ways to translate the output into reality.