Research Paper Volume 10, Issue 11 pp 3507—3527

Angiopoietin-1 and ανβ3 integrin peptide promote the therapeutic effects of L-serine in an amyotrophic lateral sclerosis/Parkinsonism dementia complex model

Hua-ying Cai 1, 2, , Ke-wei Tian 1, , Yuan-yuan Zhang 1, , Hong Jiang 3, , Shu Han 1, ,

  • 1 Institute of Anatomy and Cell Biology, Medical College, Zhejiang University, Hangzhou, China
  • 2 Department of Neurology, Sir Run Run Shaw Hospital, Medical College, Zhejiang University, Hangzhou, China
  • 3 Department of Electrophysiology, Sir Run Run Shaw Hospital, Medical College, Zhejiang University, Hangzhou, China

received: July 30, 2018 ; accepted: November 15, 2018 ; published: November 25, 2018 ;

https://doi.org/10.18632/aging.101661
How to Cite

Copyright: Cai et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult disorder of neurodegeneration that manifests as the destruction of upper and lower motor neurons. Beta-N-methylamino-L-alanine (L-BMAA), an amino acid not present in proteins, was found to cause intraneuronal protein misfolding and to induce ALS/Parkinsonism dementia complex (PDC), which presents symptoms analogous to those of Alzheimer’s-like dementia and Parkinsonism. L-serine suppresses the erroneous incorporation of L-BMAA into proteins in the human nervous system. In this study, angiopoietin-1, an endothelial growth factor crucial for vascular development and angiogenesis, and the integrin αvβ3 binding peptide C16, which inhibits inflammatory cell infiltration, were utilized to improve the local microenvironment within the central nervous system of an ALS/PDC rodent model by minimizing inflammation. Our results revealed that L-serine application yielded better effects than C16+ angiopoietin-1 treatment alone for alleviating apoptotic and autophagic changes and improving cognition and electrophysiological dysfunction, but not for improving the inflammatory micro-environment in the central nerve system, while further advances in attenuating the functional disability and pathological impairment induced by L-BMAA could be achieved by co-treatment with C16 and angiopoietin-1 in addition to L-serine. Therefore, C16+ angiopoietin-1 could be beneficial as a supplement to promote the effects of L-serine treatment.

Abbreviations

ALS-PDC: amyotrophic lateral sclerosis/Parkinson dementia complex; GSK3β: glycogen synthase kinase-3 beta; L-BMAA: beta-N-methylamino-L-alanine; TDP-43: (TAR)-DNA-binding protein 43. GLT-1: glutamate transporter 1; MN: motor neuron; SOD1: superoxide dismutase type 1; c-SEP: cortical somatosensory evoked potential; c-MEP: cortical motor-evoked potentials; GFAP: glial fibrillary acidic protein; EAE: experimental autoimmune encephalomyelitis.