ASL expression in ALDH1A1+ neurons in the substantia nigra metabolically contributes to neurodegenerative phenotype Article Swipe
Shaul Lerner
,
Raya Eilam
,
Lital N. Adler
,
Julien Baruteau
,
Topaz Kreiser
,
Michael Tsoory
,
Alexander Brandis
,
Tevie Mehlman
,
Mina Ryten
,
Juan A. Botía
,
Sonia García-Ruiz
,
Alejandro Cisterna‐García
,
Carlo Dionisi‐Vici
,
Giusy Ranucci
,
Marco Spada
,
Ram Mazkereth
,
Robert McCarter
,
Rima Izem
,
Thomas J. Balmat
,
Rachel Richesson
,
Matthias R. Baumgartner
,
Jirair K. Bedoyan
,
Susan A. Berry
,
Susan A. Berry
,
Peter Burgard
,
Lindsay C. Burrage
,
Curtis R. Coughlin
,
George A. Díaz
,
Gregory M. Enns
,
Renata C. Gallagher
,
Andrea Gropman
,
Cary O. Harding
,
Georg F. Hoffmann
,
Cynthia Le Mons
,
Shawn E. McCandless
,
J. Lawrence Merritt
,
Sandesh C.S. Nagamani
,
Andreas Schulze
,
Jennifer Seminara
,
Tamar Stricker
,
Mendel Tuchman
,
Susan E. Waisbren
,
James D. Weisfeld‐Adams
,
Derek A. Wong
,
Marc Yudkoff
,
Ehud Gazit
,
Sandesh C.S. Nagamani
,
Ayelet Erez
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1007/s00439-021-02345-5
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1007/s00439-021-02345-5
Argininosuccinate lyase (ASL) is essential for the NO-dependent regulation of tyrosine hydroxylase (TH) and thus for catecholamine production. Using a conditional mouse model with loss of ASL in catecholamine neurons, we demonstrate that ASL is expressed in dopaminergic neurons in the substantia nigra pars compacta, including the ALDH1A1 + subpopulation that is pivotal for the pathogenesis of Parkinson disease (PD). Neuronal loss of ASL results in catecholamine deficiency, in accumulation and formation of tyrosine aggregates, in elevation of α-synuclein, and phenotypically in motor and cognitive deficits. NO supplementation rescues the formation of aggregates as well as the motor deficiencies. Our data point to a potential metabolic link between accumulations of tyrosine and seeding of pathological aggregates in neurons as initiators for the pathological processes involved in neurodegeneration. Hence, interventions in tyrosine metabolism via regulation of NO levels may be therapeutic beneficial for the treatment of catecholamine-related neurodegenerative disorders.
Related Topics
Concepts
Substantia nigra
Pars compacta
Biology
Neurodegeneration
Tyrosine hydroxylase
Neuroscience
Dopaminergic
Neuromelanin
Dopamine
Parkinson's disease
Catecholamine
Internal medicine
Disease
Medicine
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1007/s00439-021-02345-5
- https://link.springer.com/content/pdf/10.1007/s00439-021-02345-5.pdf
- OA Status
- hybrid
- Cited By
- 19
- References
- 65
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3194325495
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3194325495Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1007/s00439-021-02345-5Digital Object Identifier
- Title
-
ASL expression in ALDH1A1+ neurons in the substantia nigra metabolically contributes to neurodegenerative phenotypeWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-08-21Full publication date if available
- Authors
-
Shaul Lerner, Raya Eilam, Lital N. Adler, Julien Baruteau, Topaz Kreiser, Michael Tsoory, Alexander Brandis, Tevie Mehlman, Mina Ryten, Juan A. Botía, Sonia García-Ruiz, Alejandro Cisterna‐García, Carlo Dionisi‐Vici, Giusy Ranucci, Marco Spada, Ram Mazkereth, Robert McCarter, Rima Izem, Thomas J. Balmat, Rachel Richesson, Matthias R. Baumgartner, Jirair K. Bedoyan, Susan A. Berry, Susan A. Berry, Peter Burgard, Lindsay C. Burrage, Curtis R. Coughlin, George A. Díaz, Gregory M. Enns, Renata C. Gallagher, Andrea Gropman, Cary O. Harding, Georg F. Hoffmann, Cynthia Le Mons, Shawn E. McCandless, J. Lawrence Merritt, Sandesh C.S. Nagamani, Andreas Schulze, Jennifer Seminara, Tamar Stricker, Mendel Tuchman, Susan E. Waisbren, James D. Weisfeld‐Adams, Derek A. Wong, Marc Yudkoff, Ehud Gazit, Sandesh C.S. Nagamani, Ayelet ErezList of authors in order
- Landing page
-
https://doi.org/10.1007/s00439-021-02345-5Publisher landing page
- PDF URL
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https://link.springer.com/content/pdf/10.1007/s00439-021-02345-5.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://link.springer.com/content/pdf/10.1007/s00439-021-02345-5.pdfDirect OA link when available
- Concepts
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Substantia nigra, Pars compacta, Biology, Neurodegeneration, Tyrosine hydroxylase, Neuroscience, Dopaminergic, Neuromelanin, Dopamine, Parkinson's disease, Catecholamine, Internal medicine, Disease, MedicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
19Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 1, 2024: 6, 2023: 9, 2022: 3Per-year citation counts (last 5 years)
- References (count)
-
65Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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