Adult neurogenesis and neurodegenerative diseases: A systems biology perspective
Open accessAbstract
New neurons are generated throughout adulthood in two regions of the brain, the olfactory bulb and dentate gyrus of the hippocampus, and are incorporated into the hippocampal network circuitry; disruption of this process has been postulated to contribute to neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. Known modulators of adult neurogenesis include signal transduction pathways, the vascular and immune systems, metabolic factors, and epigenetic regulation. Multiple intrinsic and extrinsic factors such as neurotrophic factors, transcription factors, and cell cycle regulators control neural stem cell proliferation, maintenance in the adult neurogenic niche, and differentiation into mature neurons; these factors act in networks of signaling molecules that influence each other during construction and maintenance of neural circuits, and in turn contribute to learning and memory. The immune system and vascular system are necessary for neuronal formation and neural stem cell fate determination. Inflammatory cytokines regulate adult neurogenesis in response to immune system activation, whereas the vasculature regulates the neural stem cell niche. Vasculature, immune/support cell populations (microglia/astrocytes), adhesion molecules, growth factors, and the extracellular matrix also provide a homing environment for neural stem cells. Epigenetic changes during hippocampal neurogenesis also impact memory and learning. Some genetic variations in neurogenesis related genes may play important roles in the alteration of neural stem cells differentiation into new born neurons during adult neurogenesis, with important therapeutic implications. In this review, we discuss mechanisms of and interactions between these modulators of adult neurogenesis, as well as implications for neurodegenerative disease and current therapeutic research. © 2016 Wiley Periodicals, Inc.
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Neurons must maintain protein homeostasis for the entire lifespan of an organism due to their extended post-mitotic state and lack of renewal and replacement.
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From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [371]
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Autophagy and ALS: mechanistic insights and therapeutic implications
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Self-citationNeural Stem Cell‐Derived Extracellular Vesicles for Advanced Neural Repair
Moretti, E. H., Lin, A. L. Y., Peruzzotti‐Jametti, L., Pluchino, S., & Mozafari, S. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70170 · Cited by 16 · see citing works
Neurogenesis and Neuroinflammation in Dialogue: Mapping Gaps, Modulating Microglia, Rewiring Aging
Tanaka, M. (2026) · Cells · doi:10.3390/cells15010078 · Cited by 11 · see citing works
- Authors
- Horgusluoglu, E., Nudelman, K., Nho, K., & Saykin, A. J.
- Affiliations
- Indiana University Indianapolis (US)
- Corresponding author
- Nho, Kwangsik
- Saykin, Andrew J.
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2016-02-16
- Volume
- 174
- Issue
- 1
- Pages
- 93-112
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC4987273
- OpenAlex
- W2274582236
- Cited by
- 174
- References
- 262
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 13 · 2023: 23 · 2022: 18 · 2021: 24 · 2020: 22 · 2019: 19 · 2018: 14 · 2017: 16 · 2016: 4
- FWCI
- 9.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institutes of Health (R01 AG19771, P30 AG10133, R00 LM011384, R01 LM011360, U01 AG024904)
- Indiana Clinical and Translational Sciences Institute (U54 RR025761, RR027710, RR020128)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- adult neurogenesis, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, dentate gyrus, olfactory bulb, neural stem cells, neural stem cell niche, neurotrophic factors, epigenetic regulation, inflammatory cytokines, microglia, astrocytes, vascular system, extracellular matrix, adhesion molecules, learning and memory
- MeSH terms
- Adult, Brain, Cell Differentiation, Cognition, Hippocampus, Humans, Neurons, Olfactory Bulb, Signal Transduction, Neurodegenerative Diseases, Epigenesis, Genetic, Systems Biology, Neurogenesis, Neural Stem Cells
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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