Molecular Pathways Involved in Frontotemporal Lobar Degeneration with TDP-43 Proteinopathy: What Can We Learn from Proteomics?
Merel O MolSuzanne S M MiedemaJohn C van SwietenJeroen G J van RooijElise G P DopperPublished in: International journal of molecular sciences (2021)
Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder clinically characterized by behavioral, language, and motor symptoms, with major impact on the lives of patients and their families. TDP-43 proteinopathy is the underlying neuropathological substrate in the majority of cases, referred to as FTLD-TDP. Several genetic causes have been identified, which have revealed some components of its pathophysiology. However, the exact mechanisms driving FTLD-TDP remain largely unknown, forestalling the development of therapies. Proteomic approaches, in particular high-throughput mass spectrometry, hold promise to help elucidate the pathogenic molecular and cellular alterations. In this review, we describe the main findings of the proteomic profiling studies performed on human FTLD-TDP brain tissue. Subsequently, we address the major biological pathways implicated in FTLD-TDP, by reviewing these data together with knowledge derived from genomic and transcriptomic literature. We illustrate that an integrated perspective, encompassing both proteomic, genetic, and transcriptomic discoveries, is vital to unravel core disease processes, and to enable the identification of disease biomarkers and therapeutic targets for this devastating disorder.
Keyphrases
- amyotrophic lateral sclerosis
- single cell
- mass spectrometry
- high throughput
- label free
- end stage renal disease
- ejection fraction
- systematic review
- endothelial cells
- newly diagnosed
- healthcare
- chronic kidney disease
- prognostic factors
- genome wide
- high resolution
- multiple sclerosis
- gene expression
- peritoneal dialysis
- single molecule
- resting state
- high performance liquid chromatography
- functional connectivity
- ms ms
- amino acid
- physical activity
- cerebral ischemia
- brain injury
- subarachnoid hemorrhage
- bioinformatics analysis