Molecular Neurobiology

, Volume 54, Issue 9, pp 7401–7459 | Cite as

Neurotrophin Signaling and Stem Cells—Implications for Neurodegenerative Diseases and Stem Cell Therapy

  • Subrata Pramanik
  • Yanuar Alan Sulistio
  • Klaus HeeseEmail author


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.


Neurotrophin BDNF NGF TRK Stem cell Alzheimer’s disease Parkinson’s disease 



This study was supported by Hanyang University and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013R1A1A2009178).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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