-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
- Cosmetic Ingredient
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Click on the blue word to follow us.
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, mainly caused by the loss of dopaminergic neurons in the substantia nigra (SN)
.
Mitochondrial function is disordered in patients with Parkinson's disease, especially mitochondrial complex I (MCI)
.
Autopsy of Parkinson's disease patients reported loss of mitochondrial DNA integrity and MCI dysfunction in substantia nigra neurons
.
In addition, mutations in genes encoding mitochondrial-related proteins (PINK1, parkin, DJ-1, and CHCHD2) have been shown to cause Parkinson's disease
.
On November 3, 2021, D.
James Surmeier's research team from the Department of Neuroscience, Feinberg School of Medicine at Northwestern University specifically knocked out Ndufs2 on dopaminergic neurons, which caused mitochondrial dysfunction and reduced dopamine release from the substantia nigra, similar to Parkinson's.
Dyskinesia, which is quite different from the current Parkinson's model
.
Researchers found that 1-month-old mice (hereinafter referred to as Ndufs2-specific knockout mice) after specifically knocking out the Ndufs2 encoding the MCI gene on dopaminergic neurons lost the ability of motor learning and showed severe fine motor dysfunction; Severe motor dysfunction began to appear after the 40th day, and then became more and more serious.
Levodopa can alleviate this dyskinesia
.
The role of mitochondria in Ndufs2-specific knockout mice on the 20th to 30th day after birth has changed: from energy producer to consumer, this is obtained from the sensitivity of the mitochondrial inner membrane (IMM) potential Further confirmed
.
Generally speaking, normal cells mainly rely on the oxidative phosphorylation of mitochondria to provide energy for the cells, but most tumor cells rely on aerobic glycolysis.
This phenomenon is called the "Warburg effect"
.
Researchers found that the substantia nigra dopaminergic neurons of Ndufs2-specific knockout mice have a similar Warburg effect: genes encoding proteins that promote glycolysis are up-regulated, and genes related to mitochondrial oxidative phosphorylation are down-regulated
.
Single-cell sequencing technology further found that Ndufs2 specifically knocked out genes related to dopaminergic neuron axon growth and transport, genes related to synaptic transmission, and gene expression related to dopamine synthesis and storage functions
.
The release of dopamine from the dendrites of dopaminergic neurons in the substantia nigra of 1 month-old Ndufs2 knockout mice is almost unaffected, and the level of tyrosine hydroxylase in this brain area has not changed, but the dopamine in the dorsolateral striatum area The release is reduced
.
In 2-month-old Ndufs2 knockout mice, the level of tyrosine hydroxylase in the dendritic region of the substantia nigra brain was reduced, and the release of dopamine was also reduced
.
The loss of axons gradually appeared after 3 months of age, and the loss of dopamine neurons did not appear until 4 months of age, showing progressive disease
.
The 1-month-old Ndufs2 knockout mice can effectively alleviate the motor learning disorder after receiving levodopa treatment, but it cannot alleviate this memory disorder in the 2-month-old Ndufs2 knockout mice
.
The reason for this result is that levodopa can promote the release of dopamine in 1-month-old Ndufs2 knockout mice, but there is no such promotion effect in 2-month-old Ndufs2 knockout mice
.
Although the dopamine release disorder in the striatum and substantia nigra of Ndufs2 knockout mice appeared at different time points, they are also important for causing motor dysfunction
.
The researchers used viral vector tools to promote the release of dopamine in the striatum and substantia nigra regions, which can effectively alleviate the dyskinesia of 3-month-old Ndufs2 knockout mice
.
In general, this article found that the mitochondria of dopamine neurons caused axon dysfunction, early motor learning disorder, fine motor disorder, and then motor dysfunction, manifested as progressive motor dysfunction
.
[References] https://doi.
org/10.
1038/s41586-021-04059-0 https://doi.
org/10.
1038/d41586-021-02955-z The pictures in the text are from the references
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, mainly caused by the loss of dopaminergic neurons in the substantia nigra (SN)
.
Mitochondrial function is disordered in patients with Parkinson's disease, especially mitochondrial complex I (MCI)
.
Autopsy of Parkinson's disease patients reported loss of mitochondrial DNA integrity and MCI dysfunction in substantia nigra neurons
.
In addition, mutations in genes encoding mitochondrial-related proteins (PINK1, parkin, DJ-1, and CHCHD2) have been shown to cause Parkinson's disease
.
On November 3, 2021, D.
James Surmeier's research team from the Department of Neuroscience, Feinberg School of Medicine at Northwestern University specifically knocked out Ndufs2 on dopaminergic neurons, which caused mitochondrial dysfunction and reduced dopamine release from the substantia nigra, similar to Parkinson's.
Dyskinesia, which is quite different from the current Parkinson's model
.
Researchers found that 1-month-old mice (hereinafter referred to as Ndufs2-specific knockout mice) after specifically knocking out the Ndufs2 encoding the MCI gene on dopaminergic neurons lost the ability of motor learning and showed severe fine motor dysfunction; Severe motor dysfunction began to appear after the 40th day, and then became more and more serious.
Levodopa can alleviate this dyskinesia
.
The role of mitochondria in Ndufs2-specific knockout mice on the 20th to 30th day after birth has changed: from energy producer to consumer, this is obtained from the sensitivity of the mitochondrial inner membrane (IMM) potential Further confirmed
.
Generally speaking, normal cells mainly rely on the oxidative phosphorylation of mitochondria to provide energy for the cells, but most tumor cells rely on aerobic glycolysis.
This phenomenon is called the "Warburg effect"
.
Researchers found that the substantia nigra dopaminergic neurons of Ndufs2-specific knockout mice have a similar Warburg effect: genes encoding proteins that promote glycolysis are up-regulated, and genes related to mitochondrial oxidative phosphorylation are down-regulated
.
Single-cell sequencing technology further found that Ndufs2 specifically knocked out genes related to dopaminergic neuron axon growth and transport, genes related to synaptic transmission, and gene expression related to dopamine synthesis and storage functions
.
The release of dopamine from the dendrites of dopaminergic neurons in the substantia nigra of 1 month-old Ndufs2 knockout mice is almost unaffected, and the level of tyrosine hydroxylase in this brain area has not changed, but the dopamine in the dorsolateral striatum area The release is reduced
.
In 2-month-old Ndufs2 knockout mice, the level of tyrosine hydroxylase in the dendritic region of the substantia nigra brain was reduced, and the release of dopamine was also reduced
.
The loss of axons gradually appeared after 3 months of age, and the loss of dopamine neurons did not appear until 4 months of age, showing progressive disease
.
The 1-month-old Ndufs2 knockout mice can effectively alleviate the motor learning disorder after receiving levodopa treatment, but it cannot alleviate this memory disorder in the 2-month-old Ndufs2 knockout mice
.
The reason for this result is that levodopa can promote the release of dopamine in 1-month-old Ndufs2 knockout mice, but there is no such promotion effect in 2-month-old Ndufs2 knockout mice
.
Although the dopamine release disorder in the striatum and substantia nigra of Ndufs2 knockout mice appeared at different time points, they are also important for causing motor dysfunction
.
The researchers used viral vector tools to promote the release of dopamine in the striatum and substantia nigra regions, which can effectively alleviate the dyskinesia of 3-month-old Ndufs2 knockout mice
.
In general, this article found that the mitochondria of dopamine neurons caused axon dysfunction, early motor learning disorder, fine motor disorder, and then motor dysfunction, manifested as progressive motor dysfunction
.
[References] https://doi.
org/10.
1038/s41586-021-04059-0 https://doi.
org/10.
1038/d41586-021-02955-z The pictures in the text are from the references
