Keywords
Dysregulations
RNA Binding Protein
Molecular Pathophysiologies
How to Cite
Abstract
Neurodegenerative diseases, characterized by the progressive degeneration and dysfunction of neurons, present significant clinical challenges, with many conditions ultimately proving fatal. Over the past few decades, extensive research has focused on developing and validating biomarkers to improve diagnosis and treatment. The repertoire of biomarkers for central nervous system (CNS) diseases has expanded to include a diverse array of biofluids, nucleic acids, and imaging modalities. However, while imaging and tissue biopsy-based indicators continue to evolve, RNA and protein biomarkers are emerging as crucial tools in the early detection and management of these diseases.
It is critical examine the key genetic biomakers, including microRNA (miRNA), long noncoding RNA (lncRNA), circulating miRNA (cimiRNA), and proteins, which holds promise for improving diagnosis and management of neurodegenerative diseases. In addition, it highlights the impending challenges related to integrating novel biomarkers into clinical practice and research.
One goal is to reduce the time, patient suffering, and cost associated with screening for neurodegenerative diseases and support identification of therapies toward improving the quality of life for patients with neurodegenerative diseases.
References
Berezovska O, Ramdya P, Skoch J, et al. Amyloid precursor protein associates with a nicastrin-dependent docking site on the presenilin 1-gamma-secretase complex in cells demonstrated by fluorescence lifetime imaging. J Neurosci 2003; 23:4560–
El-Agnaf OMA, Irvine GB. Aggregation and neurotoxicity of α-synuclein and related peptides. Biochem. Soc Trans 2001; 30:559–65
Peng, C., Trojanowski, J. Q. & Lee, V. M. Protein transmission in neurodegenerative disease. Nat. Rev. Neurol. 16, 199–212 (2020).
DeTure, M. A. & Dickson, D. W. The neuropathological diagnosis of Alzheimer’s disease. Mol. Neurodegener. 14, 32 (2019).
Villemagne, V. L. et al. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol. 12, 357–367 (2013).
Rizzo, G. et al. Accuracy of clinical diagnosis of Parkinson disease: a systematic review and meta-analysis. Neurology 86, 566–576 (2016).
Respondek, G. et al. Validation of the Movement Disorder Society criteria for the diagnosis of 4-repeat tauopathies. Mov. Disord. 35, 171–176 (2020).
Clark, C. M. et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. Lancet Neurol. 11, 669–678 (2012).
Andersen P.M. Mutation in C9orf72 changes the boundaries of ALS and FTD. Lancet Neurol. 2012;11:205–207. doi: 10.1016/S1474-4422(12)70020-0
Lin CH, Chao CC, Wu SW, Hsieh PC, Feng FP, Lin YH, Chen YM, Wu RM, Hsieh ST (2016) Pathophysiology of small-fiber sensory system in Parkinson’s disease: Skin innervation and contact heat evoked potential. Medicine (Baltimore) 95, e3058
Zis P, Grunewald RA, Chaudhuri RK, Hadjivassiliou M (2017) Peripheral neuropathy in idiopathic Parkinson’s disease: A systematic review. J Neurol Sci 378, 204–209
Merola A, Rosso M, Romagnolo A, Comi C, Fasano A, Zibetti M, Lopez-Castellanos JR, Cocito D, Lopiano L, Espay AJ (2017) Peripheral neuropathy as marker of severe Parkinson’s disease phenotype. Mov Disord 32, 1256–1258.
Cossu G, Ceravolo R, Zibetti M, Arca R, Ricchi V, Paribello A, Murgia D, Merola A, Romagnolo A, Nicoletti V, Palermo G, Mereu A, Lopiano L, Melis M, Abbruzzese G, Bonuccelli U (2016) Levodopa and neuropathy risk in patients with Parkinson disease: Effect of COMT inhibition. Parkinsonism Relat Disord 27, 81–84.
Denny JB (2006) Molecular mechanisms, biological actions, and neuropharmacology of the growth-associated protein GAP-43. Curr Neuropharmacol 4, 293–304
Edgar S., Ellis M., Abdul-Aziz N.A., Goh K.J., Shahrizaila N., Kennerson M.L., Ahmad-Annuar A. Mutation analysis of SOD1, C9orf72, TARDBP and FUS genes in ethnically-diverse Malaysian patients with amyotrophic lateral sclerosis (ALS) Neurobiol. Aging. 2021;108:200–206. doi: 10.1016/j.neurobiolaging.2021.07.008.
Doppler K, Ebert S, Uceyler N, Trenkwalder C, Ebentheuer J, Volkmann J, Sommer C (2014) Cutaneous neuropathy in Parkinson’s disease: A window into brain pathology. Acta Neuropathol 128, 99–109
Baron D.M., Fenton A.R., Saez-Atienzar S., Giampetruzzi A., Sreeram A., Shankaracharya, Keagle P.J., Doocy V.R., Smith N.J., Danielson E.W., et al. ALS-associated KIF5A mutations abolish autoinhibition resulting in a toxic gain of function. Cell Rep. 2022;39:110598. doi: 10.1016/j.celrep.2022.110598
Domingo A., Klein C. Genetics of Parkinson disease. Handb. Clin. Neurol. 2018;147:211–227. doi: 10.1016/B978-0-444-63233-3.00014-2
Rajpurkar, P., Chen, E., Banerjee, O., Topol, E. (2022). AI in health and medicine. Nature Medicine, 28: 31-38. https://doi.org/10.1038/s41591-021-01614-0
Khalif, Z., Mousa A., Hattab, M., Itmazi, J., Hassan, A., Sanugam, M., Ayyoub, A. (2023). The potential and concerns of using AI in scientific research: ChatGPT performance evaluation. JMIR Med Edu, 9:e47049.