Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo

Autor: Juha Lauren, Jaan-Olle Andressoo, Mart Saarma, Raimo K. Tuominen, Johan Peränen, Veli-Matti Leppänen, Merja H. Voutilainen, Nisse Kalkkinen, Tõnis Timmusk, Maria Lindahl, Päivi Lindholm, Sanna Janhunen
Rok vydání: 2007
Předmět:
Male
Dopamine
Mice
chemistry.chemical_compound
0302 clinical medicine
Neurotrophic factors
Glial cell line-derived neurotrophic factor
Cloning
Molecular
Conserved Sequence
In Situ Hybridization
Neurons
0303 health sciences
Multidisciplinary
biology
Dopaminergic
Brain
Parkinson Disease
3. Good health
Cell biology
Substantia Nigra
Neuroprotective Agents
Oxidopamine
medicine.drug
medicine.medical_specialty
Molecular Sequence Data
Nerve Tissue Proteins
Substantia nigra
03 medical and health sciences
Internal medicine
medicine
Animals
Humans
Amino Acid Sequence
Nerve Growth Factors
RNA
Messenger
Rats
Wistar
Cerebral dopamine neurotrophic factor
030304 developmental biology
Corpus Striatum
Rats
Disease Models
Animal
Nerve growth factor
Endocrinology
nervous system
chemistry
biology.protein
Protein Processing
Post-Translational
030217 neurology & neurosurgery
Zdroj: Nature. 448:73-77
ISSN: 1476-4687
0028-0836
Popis: In Parkinson's disease, brain dopamine neurons degenerate most prominently in the substantia nigra. Neurotrophic factors promote survival, differentiation and maintenance of neurons in developing and adult vertebrate nervous system. The most potent neurotrophic factor for dopamine neurons described so far is the glial-cell-line-derived neurotrophic factor (GDNF). Here we have identified a conserved dopamine neurotrophic factor (CDNF) as a trophic factor for dopamine neurons. CDNF, together with its previously described vertebrate and invertebrate homologue the mesencephalic-astrocyte-derived neurotrophic factor, is a secreted protein with eight conserved cysteine residues, predicting a unique protein fold and defining a new, evolutionarily conserved protein family. CDNF (Armetl1) is expressed in several tissues of mouse and human, including the mouse embryonic and postnatal brain. In vivo, CDNF prevented the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons in a rat experimental model of Parkinson's disease. A single injection of CDNF before 6-OHDA delivery into the striatum significantly reduced amphetamine-induced ipsilateral turning behaviour and almost completely rescued dopaminergic tyrosine-hydroxylase-positive cells in the substantia nigra. When administered four weeks after 6-OHDA, intrastriatal injection of CDNF was able to restore the dopaminergic function and prevent the degeneration of dopaminergic neurons in substantia nigra. Thus, CDNF was at least as efficient as GDNF in both experimental settings. Our results suggest that CDNF might be beneficial for the treatment of Parkinson's disease.
Databáze: OpenAIRE
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