Mass spectrometry based protein biomarkers and drug target discovery and clinical diagnosis in Age-Related progressing neurodegenerative diseases

Abstract

Neurodegenerative diseases correspond to overly complex health disorders that are driven by intersecting pathophysiology that are often trapped in vicious cycles of degeneration and cognitive decline. The usual diagnostic route of these diseases is based on postmortem examination that involves identifying pathology that is specific to the disease in the brain. However, in such cases, accurate diagnosis of the specific disease is limited because clinical disease presentations are often complex that do not easily allow to discriminate patient’s cognitive, behavioral, and functional impairment profiles. Additionally, an early identification and therapeutic intervention of these diseases is pivotal to slow the progression of neurodegeneration and extend healthy life span. Mass spectrometry-based techniques have proven to be hugely promising in biological sample analysis and discovery of biomarkers including protein and peptide biomarkers for potential drug target discovery. Recent studies on these biomarkers have demonstrated their potential for applications in early diagnostics and identifying therapeutic targets to battle against neurodegenerative diseases. In this review, we have presented principles of mass spectrometry (MS) and the associated workflows in analyzing and imaging biological samples for discovery of biomarkers. We have especially focused on age-related progressing neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD) and the related MS-based biomarker developments for these diseases. Finally, we present a future perspective discussing the potential research directions ahead.

Keywords:

• Neurodegeneration
• cerebrospinal fluid
• plasma
• proteomics
• biomarkers
• drug targets
• LC-MS/MS
• MALDI-TOF

Acknowledgements

IA acknowledges graduate scholarship from the Department of Biotechnology (DBT), Government of India. Financial assistance by Marie Skłodowska-Curie European Actions Individual Fellowship is thankfully acknowledged by PT.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

No funding was availed to complete this work.