Proteomics as an innovative tool to investigate frontotemporal disorders

Abstract

Neurodegenerative diseases are characterized by slow progressive loss of one or more functions of the CNS. Worldwide, the number of people affected by neurodegeneration is dramatically high and the social impact is upsetting. While being a heterogeneous group of diseases, most of these pathologies manifest similar clinical features and illness progression, thus making their diagnosis elusive. With its ability to meet the needs of neurodegenerative research, proteomics could help facilitate the diagnosis of these disorders. This strategy, recently emerged as complementary to genomics, has led in the last years to substantial achievements in deciphering molecular mechanisms and the follow-up of neurodegenerative diseases. Specifically, aim of this review is to cover the main proteomic investigations realized in the field of familial frontotemporal dementias. This disorder is less common than Alzheimer's disease and disproportionately affects younger individuals, thus representing a major psychological and economic burden for both patients and families. Although early and accurate differential diagnosis of frontotemporal dementias is crucial because of its implications for heritability, prognosis, therapeutics, and environmental management of patients, the investigative methods currently available to clinicians are incomplete. Certainly, the development of a focused therapy cannot be separated from the investigation of biochemical pathways involved in the pathogenesis.

How many proteins can be identified in a 2DE gel spot within an analysis of a complex human cancer tissue proteome?

“…A comprehensive analysis of the Hela cell proteome by SILAC 2DE‐LC‐LTQ OrbiTrap XL revealed that 676 spots from 816 analyzed ones contained at least two with up to 22 different proteins . Combined with 2DE gel image analysis, conventional 2DE‐based comparative proteomics has been extensively used to determine “differentially expressed proteins” under different physiological, pathological, or pathophysiological conditions as reviewed in the selected publications . However, the protein composition in a human tissue, cell, or body‐fluid proteome is very complex with a very wide abundance range and complicated huge protein speciation caused by splicing, truncation and modification .…”

Novel CSF biomarkers in genetic frontotemporal dementia identified by proteomics

“…7 Most studies on fluid biomarkers in FTD have used targeted approaches, allowing measurement of known protein candidates only, 7,8 while unbiased approaches have scarcely been performed. 9,10 In autosomal dominant Alzheimer's disease, unbiased approaches have uncovered early changes in the proteome. 11 In the present study, we investigated CSF proteomics by unbiased mass spectrometry (MS) in presymptomatic and symptomatic GRN mutation carriers.…”

Proteomic Analysis of Hydromethylthionine in the Line 66 Model of Frontotemporal Dementia Demonstrates Actions on Tau-Dependent and Tau-Independent Networks

“…The more recently applied endophenotype based data correlation approach appears to be more reliable [16]. However, limited proteomic studies are available for FTD (for review see [21][22][23][24][25]). For example, Hu and co-workers identified 151 differentially regulated proteins for FTD, but these only yielded 78% specificity for FTD with TDP-43 pathology (FTD-TDP) over FTD with tau pathology (FTD-tau) [26].…”