Neurotrophin Signaling and Stem Cells-Implications for Neurodegenerative Diseases and Stem Cell Therapy.
Neurotrophins (NTs) are members of a neuronal growth factor protein family whose action is mediated by the tropomyosin receptor kinase (TRK) receptor family receptors and the p75 NT receptor (p75NTR), a member of the tumor necrosis factor (TNF) receptor family. Although NTs were first discovered in neurons, recent studies have suggested that NTs and their receptors are expressed in various types of stem cells mediating pivotal signaling events in stem cell biology. The concept of stem cell therapy has already attracted much attention as a potential strategy for the treatment of neurodegenerative diseases (NDs). Strikingly, NTs, proNTs, and their receptors are gaining interest as key regulators of stem cells differentiation, survival, self-renewal, plasticity, and migration. In this review, we elaborate the recent progress in understanding of NTs and their action on various stem cells. First, we provide current knowledge of NTs, proNTs, and their receptor isoforms and signaling pathways. Subsequently, we describe recent advances in the understanding of NT activities in various stem cells and their role in NDs, particularly Alzheimer's disease (AD) and Parkinson's disease (PD). Finally, we compile the implications of NTs and stem cells from a clinical perspective and discuss the challenges with regard to transplantation therapy for treatment of AD and PD.
Graduate School of Biomedical Science and Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 133-791, Republic of Korea.
Subrata
S
Pramanik
Graduate School of Biomedical Science and Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 133-791, Republic of Korea.
Yanuar Alan
YA
Sulistio
Graduate School of Biomedical Science and Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 133-791, Republic of Korea. klaus@hanyang.ac.kr.
Klaus
http://orcid.org/0000-0002-0027-6993
K
Heese
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000628:therapy*; D020813:Receptor, trkB / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D013234:Stem Cells / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor; D020813:Receptor, trkB
Alzheimer’s disease; BDNF; NGF; Neurotrophin; Parkinson’s disease; Stem cell; TRK