User talk:Anders Lewisesquerre: Difference between revisions

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== Introduction ==

Brain-derived neurotrophic factor (BDNF) is a 13kDa signaling protein belonging to the neurotrophin family of growth factors. This family of growth factors are critical in the development, differentiation, and survival of neurons. Mammalian members of the neurotrophin family of growth factors include Nerve growth factor (NGF)

[https://www.rcsb.org/structure/6XUO PDB structure], neurotrophin-3 (NT-3) [https://www.rcsb.org/structure/1B8K PDB structure], and neurotrophin-4/5 (NT-4/5)[https://www.rcsb.org/structure/1B98 PDB structure of neurotrophin-4/5]. BDNF is primarily expressed in the brain, where it is found in the hippocampus, cortex, amygdala, and striatum, and less so in the hypothalamus. BDNF is also expressed in peripheral tissues, such as the kidneys, retina, prostate, motor neurons, skeletal muscle.

[https://www.rcsb.org/structure/6XUO PDB structure], neurotrophin-3 (NT-3) [https://www.rcsb.org/structure/1B8K PDB structure], and neurotrophin-4/5 (NT-4/5) [https://www.rcsb.org/structure/1B98 PDB structure of neurotrophin-4/5].

[[Image:BDNF_TGN_1.jpg]]

BDNF is synthesized in the Endoplasmic reticulum as a 32-35 kDa precursor (pro BDNF). This precursor is processed in the golgi-apparaturs and its terminal domain is cleaved by a convertase, the mature BDNF protein is then passed through the trans-golgi network and secreted by secretory vesicles out of the plasma membrane. BDNF is primarily expressed in the brain, where it is found in the hippocampus, cortex, amygdala, and striatum, and less so in the hypothalamus. BDNF is also expressed in peripheral tissues, such as the kidneys, retina, prostate, motor neurons, skeletal muscle.

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PLC-𝛾 is phosphorylated by BDNF binding to the TrkB receptor, leading to production of IP3 and DAG. IP3 increases intracellular calcium concentrations, and DAG regulates protein kinase C, which is important in the MAPK/ERK pathway.

[[Image:AMS-11-26363-g003.jpg]]

== Structure ==

<scene name='10/1078788/Bdnf/1'>BDNF</scene><Structure load='1b8m' size='350' frame='true' align='right' caption='BDNF' scene='10/1078788/Bdnf/1' /> is a 13kDa protein that belongs to the nerve growth factor (NGF) family. In a broader sense, BDNF is part of the cystine-knot cytokine superfamily. A cystine-knot is a structural motif characterized by three intertwined disulfide bonds that form a knot. This <scene name='10/1078788/Bdnf_disulfide_bonds_2/1'>Cystine knot</scene>, which has three disulfide bonds and is likely a key structural feature that creates ~~flding~~ necessary for binding to the TrkB receptor. The protein is composed mostly of 𝛽-sheets, with the exception of the small, <scene name='10/1078788/Bdnf_residues_22-26/1'>single alpha helical turn</scene> from amino acid residues 22-26. There are also notable <scene name='10/1078788/Bdnf_beta_turns_and_disorder/1'>flexible regions</scene> in the protein that consist of 𝛽-turns, and intrinsically disordered regions (IDRs). A ConSurf-DB analysis was done on BDNF to identify conserved sequences on the protein. The <scene name='10/1078788/BDNF_consurf/1'>Analysis results</scene> identified residues running along the long middle portions of 𝛽-sheets. This may provide insight into regions of BDNF receptor binding, where the less conserved regions may vary from species to species due to the differing physiology of such species.

<scene name='10/1078788/Bdnf/1'>BDNF</scene><Structure load='1b8m' size='350' frame='true' align='right' caption='BDNF' scene='10/1078788/Bdnf/1' /> is a 13kDa protein that belongs to the nerve growth factor (NGF) family. In a broader sense, BDNF is part of the cystine-knot cytokine superfamily. A cystine-knot is a structural motif characterized by three intertwined disulfide bonds that form a knot. This <scene name='10/1078788/Bdnf_disulfide_bonds_2/1'>Cystine knot</scene>, which has three disulfide bonds and is likely a key structural feature that creates folding necessary for binding to the TrkB receptor. The protein is composed mostly of 𝛽-sheets, with the exception of the small, <scene name='10/1078788/Bdnf_residues_22-26/1'>single alpha helical turn</scene> from amino acid residues 22-26. There are also notable <scene name='10/1078788/Bdnf_beta_turns_and_disorder/1'>flexible regions</scene> in the protein that consist of 𝛽-turns, and intrinsically disordered regions (IDRs). A ConSurf-DB analysis was done on BDNF to identify conserved sequences on the protein. The <scene name='10/1078788/BDNF_consurf/1'>Analysis results</scene> identified residues running along the long middle portions of 𝛽-sheets. This may provide insight into regions of BDNF receptor binding, where the less conserved regions may vary from species to species due to the differing physiology of such species.

== Disease ==

Implicated in multiple neurodegenerative diseases due to its apparent neuroprotective effects, ability to promote neurogenesis, and improve synaptic plasticity. Lower BDNF levels are seen in patients with Multiple Sclerosis (MS), Parkinson's disease, and Alzheimer's disease, which highlights the consequence that lower amounts of BDNF contribute to the cognitive decline seen in Alzheimer’s, and dopaminergic neuron degeneration seen in ~~parkinsons~~. ~~Hungtinton’s~~ disease, which is caused by a mutation in the huntingtin gene, produces a mutated huntingtin protein that disrupts BDNF axonal transport and transcription. Because striatal neurons heavily rely on cortically derived BDNF for survival and function, this disruption leads to the degeneration of striatal neurons, a key pathological feature of ~~Hungtington’s~~ disease. BDNF is also associated with type-2 diabetes mellitus by its regulation of energy metabolism, specifically increasing the amount of insulin secreting granules in pancreatic 𝛃 cells through TrkB ~~signal~~ pathways.

Implicated in multiple neurodegenerative diseases due to its apparent neuroprotective effects, ability to promote neurogenesis, and improve synaptic plasticity. Lower BDNF levels are seen in patients with Multiple Sclerosis (MS), Parkinson's disease, and Alzheimer's disease, which highlights the consequence that lower amounts of BDNF contribute to the cognitive decline seen in Alzheimer’s, and dopaminergic neuron degeneration seen in Parkinson's. Huntington's disease, which is caused by a mutation in the huntingtin gene, produces a mutated huntingtin protein that disrupts BDNF axonal transport and transcription. Because striatal neurons heavily rely on cortically derived BDNF for survival and function, this disruption leads to the degeneration of striatal neurons, a key pathological feature of Huntington's disease. BDNF is also associated with type-2 diabetes mellitus by its regulation of energy metabolism, specifically through increasing the amount of insulin secreting granules in pancreatic 𝛃 cells through TrkB signaling pathways.

User talk:Anders Lewisesquerre: Difference between revisions

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@@ Line 5: / Line 5: @@
 == Introduction ==
 Brain-derived neurotrophic factor (BDNF) is a 13kDa signaling protein belonging to the neurotrophin family of growth factors. This family of growth factors are critical in the development, differentiation, and survival of neurons. Mammalian members of the neurotrophin family of growth factors include Nerve growth factor (NGF)
- [https://www.rcsb.org/structure/6XUO PDB structure], neurotrophin-3 (NT-3) [https://www.rcsb.org/structure/1B8K PDB structure], and neurotrophin-4/5 (NT-4/5)[https://www.rcsb.org/structure/1B98 PDB structure of neurotrophin-4/5]. BDNF is primarily expressed in the brain, where it is found in the hippocampus, cortex, amygdala, and striatum, and less so in the hypothalamus. BDNF is also expressed in peripheral tissues, such as the kidneys, retina, prostate, motor neurons, skeletal muscle.
+[https://www.rcsb.org/structure/6XUO PDB structure], neurotrophin-3 (NT-3) [https://www.rcsb.org/structure/1B8K PDB structure], and neurotrophin-4/5 (NT-4/5) [https://www.rcsb.org/structure/1B98 PDB structure of neurotrophin-4/5].
+[[Image:BDNF_TGN_1.jpg]]
+BDNF is synthesized in the Endoplasmic reticulum as a 32-35 kDa precursor (pro BDNF). This precursor is processed in the golgi-apparaturs and its terminal domain is cleaved by a convertase, the mature BDNF protein is then passed through the trans-golgi network and secreted by secretory vesicles out of the plasma membrane. BDNF is primarily expressed in the brain, where it is found in the hippocampus, cortex, amygdala, and striatum, and less so in the hypothalamus. BDNF is also expressed in peripheral tissues, such as the kidneys, retina, prostate, motor neurons, skeletal muscle.
@@ Line 23: / Line 26: @@
 PLC-𝛾 is phosphorylated by BDNF binding to the TrkB receptor, leading to production of IP3 and DAG. IP3 increases intracellular calcium concentrations, and DAG regulates protein kinase C, which is important in the MAPK/ERK pathway.
+[[Image:AMS-11-26363-g003.jpg]]
 == Structure ==
-<scene name='10/1078788/Bdnf/1'>BDNF</scene><Structure load='1b8m' size='350' frame='true' align='right' caption='BDNF' scene='10/1078788/Bdnf/1' /> is a 13kDa protein that belongs to the nerve growth factor (NGF) family. In a broader sense, BDNF is part of the cystine-knot cytokine superfamily. A cystine-knot is a structural motif characterized by three intertwined disulfide bonds that form a knot. This <scene name='10/1078788/Bdnf_disulfide_bonds_2/1'>Cystine knot</scene>, which has three disulfide bonds and is likely a key structural feature that creates flding necessary for binding to the TrkB receptor. The protein is composed mostly of 𝛽-sheets, with the exception of the small, <scene name='10/1078788/Bdnf_residues_22-26/1'>single alpha helical turn</scene> from amino acid residues 22-26. There are also notable <scene name='10/1078788/Bdnf_beta_turns_and_disorder/1'>flexible regions</scene> in the protein that consist of 𝛽-turns, and intrinsically disordered regions (IDRs). A ConSurf-DB analysis was done on BDNF to identify conserved sequences on the protein. The <scene name='10/1078788/BDNF_consurf/1'>Analysis results</scene> identified residues running along the long middle portions of 𝛽-sheets. This may provide insight into regions of BDNF receptor binding, where the less conserved regions may vary from species to species due to the differing physiology of such species.
+<scene name='10/1078788/Bdnf/1'>BDNF</scene><Structure load='1b8m' size='350' frame='true' align='right' caption='BDNF' scene='10/1078788/Bdnf/1' /> is a 13kDa protein that belongs to the nerve growth factor (NGF) family. In a broader sense, BDNF is part of the cystine-knot cytokine superfamily. A cystine-knot is a structural motif characterized by three intertwined disulfide bonds that form a knot. This <scene name='10/1078788/Bdnf_disulfide_bonds_2/1'>Cystine knot</scene>, which has three disulfide bonds and is likely a key structural feature that creates folding necessary for binding to the TrkB receptor. The protein is composed mostly of 𝛽-sheets, with the exception of the small, <scene name='10/1078788/Bdnf_residues_22-26/1'>single alpha helical turn</scene> from amino acid residues 22-26. There are also notable <scene name='10/1078788/Bdnf_beta_turns_and_disorder/1'>flexible regions</scene> in the protein that consist of 𝛽-turns, and intrinsically disordered regions (IDRs). A ConSurf-DB analysis was done on BDNF to identify conserved sequences on the protein. The <scene name='10/1078788/BDNF_consurf/1'>Analysis results</scene> identified residues running along the long middle portions of 𝛽-sheets. This may provide insight into regions of BDNF receptor binding, where the less conserved regions may vary from species to species due to the differing physiology of such species.
 == Disease ==
-Implicated in multiple neurodegenerative diseases due to its apparent neuroprotective effects, ability to promote neurogenesis, and improve synaptic plasticity. Lower BDNF levels are seen in patients with Multiple Sclerosis (MS), Parkinson's disease, and Alzheimer's disease, which highlights the consequence that lower amounts of BDNF contribute to the cognitive decline seen in Alzheimer’s, and dopaminergic neuron degeneration seen in parkinsons. Hungtinton’s disease, which is caused by a mutation in the huntingtin gene, produces a mutated huntingtin protein that disrupts BDNF axonal transport and transcription. Because striatal neurons heavily rely on cortically derived BDNF for survival and function, this disruption leads to the degeneration of striatal neurons, a key pathological feature of Hungtington’s disease. BDNF is also associated with type-2 diabetes mellitus by its regulation of energy metabolism, specifically increasing the amount of insulin secreting granules in pancreatic 𝛃 cells through TrkB signal pathways.
+Implicated in multiple neurodegenerative diseases due to its apparent neuroprotective effects, ability to promote neurogenesis, and improve synaptic plasticity. Lower BDNF levels are seen in patients with Multiple Sclerosis (MS), Parkinson's disease, and Alzheimer's disease, which highlights the consequence that lower amounts of BDNF contribute to the cognitive decline seen in Alzheimer’s, and dopaminergic neuron degeneration seen in Parkinson's. Huntington's disease, which is caused by a mutation in the huntingtin gene, produces a mutated huntingtin protein that disrupts BDNF axonal transport and transcription. Because striatal neurons heavily rely on cortically derived BDNF for survival and function, this disruption leads to the degeneration of striatal neurons, a key pathological feature of Huntington's disease. BDNF is also associated with type-2 diabetes mellitus by its regulation of energy metabolism, specifically through increasing the amount of insulin secreting granules in pancreatic 𝛃 cells through TrkB signaling pathways.