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.
Bibliographical noteFunding Information:
Funding: We would like to thank the funding agencies for this project; the Dutch Organization for Scientific Research (NWO) through the ZonMw Memorabel grant (project #733050811), the Alz‐ heimer Netherlands organization, and the Gieskes‐Strijbis Foundation.
We would like to thank the funding agencies for this project; the Dutch Organization for Scientific Research (NWO) through the ZonMw Memorabel grant (project #733050811), the Alzheimer Netherlands organization, and the Gieskes?Strijbis Foundation.
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright 2021 Elsevier B.V., All rights reserved.
- Frontotemporal dementia
- Frontotemporal lobar degeneration
- Mass spectrometry