Exosomal Angiogenin as a Potential Biomarker in Amyotrophic Lateral Sclerosis
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ICAL NEUROCHEMISTRY
Exosomal Angiogenin as a Potential Biomarker in Amyotrophic Lateral Sclerosis M. V. Ivanovaa, 1, E. O. Chekanovaa, B. V. Beluginb, I. V. Dolzhikovab, I. L. Tutykhinab, and M. N. Zakharovaa aResearch
Center for Neurology, Moscow, Russia Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences, Moscow, Russia
b
Received January 6, 2020; revised January 8, 2020; accepted January 9, 2020
Abstract—Exosomes are extracellular vesicles that represent an important mode of intercellular communication. It is thought that exosomes can carry biologically active molecules associated with the progressive spreading of amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disease characterized by the progressive death of motor neurons. Angiogenin is likely to be important in the pathogenesis of ALS. This paper analyzes the content of angiogenin in blood plasma, CSF, and exosome fractions obtained from blood plasma and CSF in ALS. The study included 30 patients with ALS and 26 age and gender matched healthy controls. The relative amount of angiogenin in plasma and CSF was significantly higher than in exosome fractions (p < 0.05). A comparison of angiogenin content in plasma and exosome fraction revealed lower angiogenin levels in patients with ALS compared to healthy volunteers (p < 0.05), which may indicate a protective role of angiogenin. Higher concentrations of angiogenin in plasma and its exosome fractions tended to correlate with better functional states in patients. Therefore, a reduction of angiogenin levels in plasma and the exosome fraction from plasma may be a marker of disease progression, but these data need to be confirmed in a larger cohort. Keywords: amyotrophic lateral sclerosis, motor neuron disease, neurodegeneration, angiogenin, exosomes, neuroprotection DOI: 10.1134/S1819712420030058
INTRODUCTION Angiogenin was first isolated in 1985 from culture medium conditioned by human colon adenocarcinoma cells (HT-29) and was identified based on its angiogenic capacity. The mature angiogenin is a basic, single-chain protein containing 123 amino acids with a molecular weight of about 14.4 kDa [1]. Angiogenin has also been implicated in neurogenesis [2], neuroprotection [3], and immunoregulation [4]. It belongs to the RNase superfamily [1], and undergoes nuclear translocation and activates ribosomal RNA transcription [5]. It may promote degradation of the basement membrane [6] and activate signal transduction pathways [5, 7], triggering the release of several biologically active factors. In addition, angiogenin has been shown to play a role in the pathogenesis of some diseases, including tumors [8], Parkinson’s disease [9], and amyotrophic lateral sclerosis (ALS). ALS is a progressive and fatal neurodegenerative disease that primarily affects motor neurons. The disease is highly variable in rates of progression; the 1 Corresponding
author; address: Volokolamskoe shosse 80, Moscow, 125367 Russia; phone: 8(495)490-24-10; e-mail: [email protected].
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