Abstract
Adult hippocampal neurogenesis is a multistage mechanism that continues
throughout the lifespan of human and non-human mammals. These adult-born neurons in
the central nervous system (CNS) play a significant role in various hippocampus-dependent
processes, including learning, mood regulation, pattern recognition, etc. Reduction
of adult hippocampal neurogenesis, caused by multiple factors such as neurological disorders
and aging, would impair neuronal proliferation and differentiation and result in memory
loss. Accumulating studies have indicated that functional neuron impairment could
be restored by promoting adult hippocampal neurogenesis. In this review, we summarized
the small molecules that could efficiently promote the process of adult neurogenesis,
particularly the agents that have the capacity of crossing the blood-brain barrier (BBB),
and showed in vivo efficacy in mammalian brains. This may pave the way for the rational
design of drugs to treat human neurodegenerative disorders in the future.
Keywords:
Neurogenesis, hippocampus, neurodegenerative, small molecules, structure-activity relationship, human brain.
[104]
Jolivalt, C.G.; Marquez, A.; Anaya, C.; Kifle, B.; Muttalib, N.; Hefferan, M.; Johe, K.; Calcutt, N.A. Therapeutic efficacy of NSI-189 against diabetic neuropathy and encephalopathy in mice. Diabetes, 2017, 66, A145-A145.
[106]
English, B.; Johnstone, J.; Johe, K.; Gertsik, L.; Sherman, M.; Fava, M.; Ereshefsky, L. Effects of NSI-189, a neurogenic compound, on quantitative electroencephalography (qEEG) in patients with major depressive disorder (MDD) during a phase 1b randomized, double-blind, placebo controlled, multiple ascending dose study. Int. J. Neuropsychopharmacol., 2014, 17, 119.
[107]
Ereshefsky, L.; English, B.; Johnstone, J.; Johe, K.; Gertsik, L.; Fava, M.; Freeman, M.; Potkin, S. Effects of NSI-189, a neurogenic compound, on Quantitative EEQ (QEEG) in patients with major depressive disorder: QEEG effects, dose response relationships, and clinical outcomes. Neuropsychopharmacology, 2014, 39, S353-S354.
[110]
Papakostas, G.; Johe, K.; Hoeppner, B.; Freeman, M.; Flynn, M.; Hand, H.; Kashambwa, R.; Fava, M. A phase 2, double-blind, placebo-controlled study of NSI-189 phosphate, a neurogenic compound among out-patients with major depressive disorder. Neuropsychopharmacology, 2017, 42, S162-S163.