Role of heparin binding growth factors in nigrostriatal dopamine system development and Parkinson's disease
Abstract
The developmental biology of the dopamine (DA) system may hold important clues to its reconstruction. We hypothesized that factors highly expressed during nigrostriatal development and re-expressed after injury and disease may play a role in protection and reconstruction of the nigrostriatal system. Examination of gene expression in the developing striatum suggested an important role for the heparin binding growth factor family at time points relevant to establishment of dopaminergic innervation. Midkine, pleiotrophin (PTN), and their receptors syndecan-3 and receptor protein tyrosine phosphatase beta/zeta, were highly expressed in the striatum during development. Furthermore, PTN was up-regulated in the degenerating substantia nigra of Parkinson's patients. The addition of PTN to ventral mesencephalic cultures augmented DA neuron survival and neurite outgrowth. Thus, PTN was identified as a factor that plays a role in the nigrostriatal system during development and in response to disease, and may therefore be useful for neuroprotection or reconstruction of the DA system.
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Elevated PTN is detected in the substantia nigra of patients with Parkinson's disease and in the CSF of patients with AD.
“Elevated PTN is detected in the substantia nigra of patients with Parkinson's disease and in the cerebrospinal fluid (CSF) of patients with AD. 41 , 42”
From Loss of <i>Inpp5d</i> has disease‐relevant and sex‐specific effects on glial transcriptomes (2024) · cites this paper as [41]
Cites
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The midkine family of growth factors: diverse roles in nervous system formation and maintenance
Winkler, C., & Yao, S. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12462 · Cited by 72 · see citing works
Loss of <i>Inpp5d</i> has disease‐relevant and sex‐specific effects on glial transcriptomes
Dabin, L. C., Kersey, H., Kim, B., Acri, D. J., Sharify, D., Lee‐Gosselin, A., Lasagna‐Reeves, C. A., Oblak, A. L., Lamb, B. T., & Kim, J. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13901 · Cited by 10 · see citing works
“41,42 Accumulating evidence points to astrocyte-derived PTN as an anti-inflammatory, neuroprotective factor secreted by reactive astrocytes.”
- Authors
- Marchionini, D. M., Lehrmann, E., Chu, Y., He, B., Sortwell, C. E., Becker, K. G., Freed, W. J., Kordower, J. H., & Collier, T. J.
- Affiliations
- Rush University Medical Center (US)
- National Institutes of Health (US)
- Corresponding author
- Marchionini, Deanna M.
- ORCID
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 1147
- Pages
- 77-88
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2033290532
- Cited by
- 69
- References
- 3
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 3 · 2013: 4 · 2012: 7
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns042125-04)
- National Institute of Neurological Disorders and Stroke (NS42125)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- heparin-binding growth factors, nigrostriatal dopamine system, Parkinson's disease, midkine, pleiotrophin, syndecan-3, striatal development, dopaminergic neuron survival, neurite outgrowth, neuroprotection, substantia nigra degeneration, ventral mesencephalon
- MeSH terms
- Midkine, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Carrier Proteins, Dopamine, Female, Gene Expression Regulation, Humans, Male, Parkinson Disease, Rats, Inbred F344, Reference Values, Substantia Nigra, Supranuclear Palsy, Progressive, Case-Control Studies, Cytokines, Neostriatum, Receptor Protein-Tyrosine Kinases, Rats, Syndecan-3
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