Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Apr 5:16:853911.
doi: 10.3389/fnins.2022.853911. eCollection 2022.

Mitochondria and Other Organelles in Neural Development and Their Potential as Therapeutic Targets in Neurodegenerative Diseases

Shuyuan Zhang  1 , Juan Zhao  2 , Zhenzhen Quan  1 , Hui Li  1 , Hong Qing  1
Affiliations
Review

Mitochondria and Other Organelles in Neural Development and Their Potential as Therapeutic Targets in Neurodegenerative Diseases

Shuyuan Zhang et al. Front Neurosci. .

Abstract

The contribution of organelles to neural development has received increasing attention. Studies have shown that organelles such as mitochondria, endoplasmic reticulum (ER), lysosomes, and endosomes play important roles in neurogenesis. Specifically, metabolic switching, reactive oxygen species production, mitochondrial dynamics, mitophagy, mitochondria-mediated apoptosis, and the interaction between mitochondria and the ER all have roles in neurogenesis. Lysosomes and endosomes can regulate neurite growth and extension. Moreover, metabolic reprogramming represents a novel strategy for generating functional neurons. Accordingly, the exploration and application of mechanisms underlying metabolic reprogramming will be beneficial for neural conversion and regenerative medicine. There is adequate evidence implicating the dysfunction of cellular organelles-especially mitochondria-in neurodegenerative disorders, and that improvement of mitochondrial function may reverse the progression of these diseases through the reinforcement of adult neurogenesis. Therefore, these organelles have potential as therapeutic targets for the treatment of neurodegenerative diseases. In this review, we discuss the function of these organelles, especially mitochondria, in neural development, focusing on their potential as therapeutic targets in neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis.

Keywords: antioxidants; metabolic reprogramming; mitochondira; neural development; neurodegenerative disease.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) In the subventricular zone (SVZ), NSCs, also called radial glia-like cells, gradually differentiate into transient amplifying progenitor cells and neuroblasts. (B) In the subgranular zone (SGZ), radial glia-like cells differentiate into non-radial progenitor cells, intermediate progenitor cells (IPCs), and neuroblasts. The latter become mature excitatory granule neurons, which gradually migrate to the granule cell layer and extend their dendrites toward the molecular layer in the hippocampus. (C) Adult neural stem cells (NSCs) can exit or enter the cell cycle through changing between quiescence and activated states. Once activated, NSCs can divide either symmetrically or asymmetrically. Neural progenitor cells (NPCs) can further differentiate into three cell types: neurons, astrocytes, and oligodendrocytes.
FIGURE 2
FIGURE 2
Mitochondria participate in neural differentiation in neural stem cells (NSCs) and committed cells. (A) Intermediate metabolites generated in the tricarboxylic acid (TCA) cycle, such as α–ketoglutarate (αKG), can regulate neurogenesis through histone/DNA demethylation for the maintenance of stem cell pluripotency. Reactive oxygen species (ROS) generated through NADPH-oxidase (NOX) can regulate the proliferation of NSCs via the PI3K/AKT pathway. (B) In committed cells, the metabolic pattern gradually switches from glycolysis to oxidative phosphorylation (OXPHOS). ROS generated through the electron transport chain (ETC) can activate self-renewal-inhibiting and neural differentiation-promoting genes via NRF2-dependent retrograde signaling. In contrast, ROS can also facilitate the SIRT1-mediated inhibition of Mash1 expression, thereby guiding NPCs to an astroglial fate.
FIGURE 3
FIGURE 3
Endosome trafficking is involved in the regulation of neural plasticity. NGF-TrkA recycling endosomes can be retrogradely transported from the axon to the cell body and mediate the activation of genes related to axon outgrowth and neural differentiation, such as CREB. In addition, TrkA receptors can also be transported anterogradely from the plasma membrane at the soma to axon terminals via Rab11-positive recycling endosomes. Moreover, NGF-TrkA signaling endosomes can function at local axon tips to regulate axon growth. NGF-TrkA endosomes can promote synaptic maintenance through the aggregation of postsynaptic density clusters in dendrites.
FIGURE 4
FIGURE 4
Mitochondrial pharmacology in neurodegenerative diseases. The downregulation of NAD(+) following DNA damage results in decreased SIRT1 activity, which leads to decreased deacetylation of FOXO, p53, and NF-κB and elevated levels of reactive oxygen species (ROS). This results in increased autophagy, cell cycle arrest, apoptosis, inflammation, and further DNA damage, finally leading to neurodegenerative disease. Several metabolic and mitochondria-targeted antioxidants have been developed to increase NAD(+) levels and reduce those of ROS.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Adhihetty P. J., Beal M. F. (2008). Creatine and its potential therapeutic value for targeting cellular energy impairment in neurodegenerative diseases. Neuromolecular. Med. 10 275–290. 10.1007/s12017-008-8053-y - DOI - PMC - PubMed
    1. Adusumilli V. S., Walker T. L., Overall R. W., Klatt G. M., Zeidan S. A., Zocher S., et al. (2021). ROS dynamics delineate functional states of hippocampal neural stem cells and link to their activity-dependent exit from quiescence. Cell Stem Cell 28 300–314e6. 10.1016/j.stem.2020.10.019 - DOI - PMC - PubMed
    1. Ahlqvist K. J., Hamalainen R. H., Yatsuga S., Uutela M., Terzioglu M., Gotz A., et al. (2012). Somatic progenitor cell vulnerability to mitochondrial DNA mutagenesis underlies progeroid phenotypes in Polg mutator mice. Cell Metab. 15 100–109. 10.1016/j.cmet.2011.11.012 - DOI - PubMed
    1. Ahn E. H., Lei K., Kang S. S., Wang Z. H., Liu X., Hong W., et al. (2021). Mitochondrial dysfunction triggers the pathogenesis of Parkinson’s disease in neuronal C/EBPbeta transgenic mice. Mol. Psychiatry 26 7838–7850. 10.1038/s41380-021-01284-x - DOI - PubMed
    1. Arduino D. M., Esteves A. R., Cortes L., Silva D. F., Patel B., Grazina M., et al. (2012). Mitochondrial metabolism in Parkinson’s disease impairs quality control autophagy by hampering microtubule-dependent traffic. Hum. Mol. Genet. 21 4680–4702. 10.1093/hmg/dds309 - DOI - PMC - PubMed

LinkOut - more resources