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.