Neurodegenerative diseases are devastating medical conditions associated with substantial neuronal loss and alterations in neuronal replacement via neurogenesis in specific regions of the central nervous system. The etiology and pathogenesis of most of these conditions are still obscure. However, evidence has shown that neuro-inflammation, oxidative stress, and abnormal protein deposition in neural tissue play a critical role in the degenerative process with the ultimate result at the cellular level being the loss of neurons and other cells in the brain. Conversely, neurogenesis is the process by which new neurons are formed from populations of neural stem or progenitor cells residing in distinct regions of the CNS: the subventricular zone (SVZ)/olfactory bulb (OB) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). Neurogenesis occurs in four main stages: maintenance and proliferation of quiescent adult neural stem cells (NSCs); fate specification; differentiation, maturation, and survival of the immature neurons; and integration into the existing brain circuit. All of these processes play a central role in neurogenesis and contribute to the success of regenerating CNS tissue in neurodegenerative states as newly formed neurons display functional properties indistinguishable from mature neurons. Furthermore, evidence on a behavioural level has suggested that neurogenesis in the adult CNS is essential in processes such as memory and learning. Therefore, pharmacological modulation of the process of neuronal renewal via neurogenesis represents a hopeful therapeutic strategy to treat neurodegenerative diseases.

Therapeutic approaches preventing neuronal loss are limited due to the protective nature of the blood-brain barrier that hampers drug targeting toward neurons. Some plant metabolites presumably cross the blood-brain barrier. There is a wide range of signalling pathways used by plant extracts to act on the nervous system: interaction with receptors, transcription factors, growth factors, inflammatory processes, protein kinases, protein phosphatases, and oxidative balance. Transcription factors as well as growth factors and enzymes modulate the pathways controlling synaptic plasticity and therefore neurogenesis. However, the direct impact of plants on neurogenesis remains subject to controversy. Are the modifications induced by secondary metabolites derived from plants capable of causing noticeable and predictable modifications on the health? Is this contribution likely to significantly impact progress in neurodegenerative disease therapy? The answer to these questions remains to be fully justified.

The aim of this Special Issue is to collate research related to advances in the field of plant secondary metabolites, neurogenesis, and neurodegenerative disorders therapy. Original research and review articles are welcome.

Potential topics include but are not limited to the following:

• Secondary metabolites, neurogenesis, and neurodegenerative diseases
• Stem cells
• Learning and memory
• Neuro-inflammation
• Oxidative stress in the CNS
• Ageing and neurogenesis
• Environment enrichment
• Depression, antidepressants, and neurogenesis