Biomarkers and the Role of α-Synuclein in Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the presence of α-synuclein (α-Syn)-rich Lewy bodies (LBs) and the preferential loss of dopaminergic (DA) neurons in the substantia nigra (SN) pars compacta (SNpc). However, the widespread involvement of other central nervous systems (CNS) structures and peripheral tissues is now widely documented. The onset of the molecular and cellular neuropathology of PD likely occurs decades before the onset of the motor symptoms characteristic of PD, so early diagnosis of PD and adequate tracking of disease progression could significantly improve outcomes for patients. Because the clinical diagnosis of PD is challenging, misdiagnosis is common, which highlights the need for disease-specific and early-stage biomarkers. This review article aims to summarize useful biomarkers for the diagnosis of PD, as well as the biomarkers used to monitor disease progression. This review article describes the role of α-Syn in PD and how it could potentially be used as a biomarker for PD. Also, preclinical and clinical investigations encompassing genetics, immunology, fluid and tissue, imaging, as well as neurophysiology biomarkers are discussed. Knowledge of the novel biomarkers for preclinical detection and clinical evaluation will contribute to a deeper understanding of the disease mechanism, which should more effectively guide clinical applications.

Probing the Pre-diagnostic Phase of Parkinson's Disease in Population-Based Studies

“…During the preclinical phase, however, no symptoms of disease have yet arisen (2). Currently, the predictive ability of preclinical biomarkers for future PD diagnosis is limited, but research is ongoing (4,11,19,20). Promising biomarkers for early detection and diagnosis of PD include α-synuclein measurements in the cerebrospinal fluid, blood and peripheral tissue (11,19,20).…”

“…Currently, the predictive ability of preclinical biomarkers for future PD diagnosis is limited, but research is ongoing (4,11,19,20). Promising biomarkers for early detection and diagnosis of PD include α-synuclein measurements in the cerebrospinal fluid, blood and peripheral tissue (11,19,20). Furthermore, as dopamine loss occurs steadily throughout pre-diagnostic PD (2,21,22), dopamine transporter scanning might be used as an imaging marker of the early phases of PD (11,20).…”

“…Furthermore, both PD and AD require easy-to-measure preclinical biomarkers for earlier disease recognition and recruitment of participants in trials (4,11,19,(75)(76)(77)(78). AD research has shown the benefit of considering distinct biomarkers at different disease phases (78,79) and of creating panels of multiple biomarkers (78,79).…”

The Impact of SNCA Variations and Its Product Alpha-Synuclein on Non-Motor Features of Parkinson’s Disease

“…PD pathology is characterized by loss of dopaminergic neurons in the midbrain substantia nigra with consequent accumulation of Lewy bodies (LB) in the surviving neurons [ 12 ]. The main component of LB is represented by the protein alpha-synuclein (α-syn), whose aggregation and accumulation perpetuates neuronal degeneration [ 13 ]. A-syn is expressed not only in the central nervous system, where it represents about 1% of all cytosolic proteins, but also in peripheral regions, contributing to the great variety of non-motor symptoms commonly seen in PD patients [ 14 ].…”

In Situ Continuous Wave Electron Paramagnetic Resonance Investigation of the Amyloid Aggregation of Parkinson’s Protein Alpha-Synuclein—the Second Spin-Label Position

“…The protein αS contains 140 aminoacids residues, lacks secondary structure in solution, and therefore is classified as an intrinsically disordered protein (IDP). It gained notoriety because of its putative role in Parkinson's disease [5,6] and consists of the amphipatic region of residues 1-100, involved in membrane binding that also contains the NAC (non-amyloid-beta component) residues 61-95, and the negatively charged C-terminus, from residue 100 onwards [7].…”