Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers
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(2020) 15:58
REVIEW
Open Access
Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers Elisabetta Zucchi1, Valentina Bonetto2, Gianni Sorarù3,4, Ilaria Martinelli5, Piero Parchi6,7, Rocco Liguori6,8 and Jessica Mandrioli5*
Abstract Motor neuron diseases (MNDs) are etiologically and biologically heterogeneous diseases. The pathobiology of motor neuron degeneration is still largely unknown, and no effective therapy is available. Heterogeneity and lack of specific disease biomarkers have been appointed as leading reasons for past clinical trial failure, and biomarker discovery is pivotal in today’s MND research agenda. In the last decade, neurofilaments (NFs) have emerged as promising biomarkers for the clinical assessment of neurodegeneration. NFs are scaffolding proteins with predominant structural functions contributing to the axonal cytoskeleton of myelinated axons. NFs are released in CSF and peripheral blood as a consequence of axonal degeneration, irrespective of the primary causal event. Due to the current availability of highly-sensitive automated technologies capable of precisely quantify proteins in biofluids in the femtomolar range, it is now possible to reliably measure NFs not only in CSF but also in blood. In this review, we will discuss how NFs are impacting research and clinical management in ALS and other MNDs. Besides contributing to the diagnosis at early stages by differentiating between MNDs with different clinical evolution and severity, NFs may provide a useful tool for the early enrolment of patients in clinical trials. Due to their stability across the disease, NFs convey prognostic information and, on a larger scale, help to stratify patients in homogenous groups. Shortcomings of NFs assessment in biofluids will also be discussed according to the available literature in the attempt to predict the most appropriate use of the biomarker in the MND clinic. Keywords: Amyotrophic lateral sclerosis, Motor neuron disorder, Neurofilament, Biomarkers, Diagnostic, Prognostic, Disease-progression, Sensitivity
Background Amyotrophic Lateral Sclerosis (ALS), the most prevalent among motor neuron disorders (MNDs), usually affects the motor system at both central and peripheral levels. However, the disease may also selectively or differentially involve the upper or lower motor neurons (respectively UMN and LMN), and may even include an extra-motor * Correspondence: [email protected] 5 Department of Neurosciences, Azienda Ospedaliero Universitaria Modena, Modena, Italy Full list of author information is available at the end of the article
dimension, leading to behavioural and cognitive dysfunction [1–3]. Expanded knowledge of the genotypic and phenotypic variability of the disease suggests the possibility of different pathogenic trajectories, which would explain, for example, the existence of certain extremes within MND spectrum with selective UMN or LMN involvement and slower progression, such as primary lateral sclerosis (PLS) or progressive muscula
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