Neurotrophin

Identifiers
Symbol	NGF
Pfam	PF00243
InterPro	IPR002072
PROSITE	PDOC00221
SCOP	1bet
SUPERFAMILY	1bet
Available protein structures: Pfam structures PDB RCSB PDB; PDBe PDBsum structure summary

Neurotrophins are a family of proteins that induce the survival,^[1] development, and function^[2] of neurons.

They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow.^[3] Growth factors such as neurotrophins that promote the survival of neurons are known as neurotrophic factors. Neurotrophic factors are secreted by target tissue and act by preventing the associated neuron from initiating programmed cell death - thus allowing the neurons to survive. Neurotrophins also induce differentiation of progenitor cells, to form neurons.

Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain (for example, the hippocampus) retain the ability to grow new neurons from neural stem cells^{[citation needed]}, a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis.

Terminology[link]

The term neurotrophin may be used as a synonym for neurotrophic factor,^[4] but the term neurotrophin is more generally reserved for four structurally related factors: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), with neurotrophic factor additionally referring to the GDNF family of ligands and ciliary neurotrophic factor (CNTF).^{[citation needed]}

Function[link]

During the development of the vertebrate nervous system, many neurons become redundant (because they have died, failed to connect to target cells, etc.) and are eliminated. At the same time, developing neurons send out axon outgrowths that contact their target cells.^[5] Such cells control their degree of innervation (the number of axon connections) by the secretion of various specific neurotrophic factors that are essential for neuron survival. One of these is nerve growth factor (NGF or beta-NGF), a vertebrate protein that stimulates division and differentiation of sympathetic and embryonic sensory neurons.^[6][7] NGF is mostly found outside the central nervous system (CNS), but slight traces have been detected in adult CNS tissues, although a physiological role for this is unknown.^[5] It has also been found in several snake venoms.^[8][9]

In the peripheral and central neurons, neurotrophins are important regulators for survival, differentiation, and maintenance of nerve cells. They are small proteins that secrete into the nervous system to help keep nerve cells alive. There are two distinct classes of glycosylated receptors that can bind to neurotrophins. These two proteins are p75 (NTR), which binds to all neurotrophins, and subtypes of Trk, which are only specific for each different neurotrophins. The reported structure above is a 2.6 Å-resolution crystal structure of neurotrophin-3 (NT-3) complex to the ectodomain of glycosylated p75 (NRT), forming a symmetrical crystal structure. This is different to other studies which shows a dimer of nerve growth factor (NGF) bound to a single ectodomain of deglycosylated p75(NTR), resulting in an asymmetrical crystal structure. The crystal structure of NT-3 shows that NT-3 forms a central homodimer around which two glycosylated p75 (NRT) molecules bind symmetrically. The symmetrical binding takes place along the NT-3 interfaces, resulting in a 2:2 ligand-receptor cluster in the center. The symmetrical and asymmetrical structures show that there is a significant difference in ligand-receptor interactions and p75 (NRT) conformations. This symmetrical complex indicates that p75(NRT) activates at the cell surface. In addition, this symmetrical crystal structure provides a model for NTs-p75(NTR) recognition and signal generation, as well as insights into coordination between p75(NTR) and Trks.^[10]

Structure[link]

NGF is a protein of about 120 residues that is cleaved from a larger precursor molecule. It contains six cysteines all involved in intrachain disulfide bonds. A schematic representation of the structure of NGF is shown below:

                                   +------------------------+
                                   |                        |
                                   |                        |
       xxxxxxCxxxxxxxxxxxxxxxxxxxxxCxxxxCxxxxxCxxxxxxxxxxxxxCxCxxxx
             |                          |     |               |
             +--------------------------|-----+               |
                                        +---------------------+

where 'C': conserved cysteine involved in a disulfide bond.

Receptors[link]

Main article: Nerve growth factor receptor

There are two classes of receptors for neurotrophins: p75 and the "Trk" family of Tyrosine kinases receptors.^[11]

Types[link]

Nerve growth factor[link]

Nerve growth factor (NGF), the prototypical growth factor, is a protein secreted by a neuron's target cell. NGF is critical for the survival and maintenance of sympathetic and sensory neurons. NGF is released from the target cells, binds to and activates its high affinity receptor TrkA on the neuron, and is internalized into the responsive neuron. The NGF/TrkA complex is subsequently trafficked back to the neuron's cell body. This movement of NGF from axon tip to soma is thought to be involved in the long-distance signaling of neurons^{[citation needed]}.

Brain-derived neurotrophic factor[link]

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor found originally in the brain, but also found in the periphery. To be specific, it is a protein that has activity on certain neurons of the central nervous system and the peripheral nervous system; it helps to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses through axonal and dendritic sprouting. In the brain, it is active in the hippocampus, cortex, cerebellum, and basal forebrain — areas vital to learning, memory, and higher thinking. BDNF is the second neurotrophic factor to be characterized, after NGF and before neurotrophin-3.

BDNF is one of the most active substances to stimulate neurogenesis. Mice born without the ability to make BDNF suffer developmental defects in the brain and sensory nervous system, and usually die soon after birth, suggesting that BDNF plays an important role in normal neural development.

Despite its name, BDNF is actually found in a range of tissue and cell types, not just the brain. Expression can be seen in the retina, the CNS, motor neurons, the kidneys, and the prostate.

Neurotrophin-3[link]

Neurotrophin-3, or NT-3, is a neurotrophic factor, in the NGF-family of neurotrophins. It is a protein growth factor that has activity on certain neurons of the peripheral and central nervous system; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons and synapses. NT-3 is the third neurotrophic factor to be characterized, after NGF and BDNF.

NT-3 is unique among the neurotrophins in the number of neurons it has potential to stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC and TrkB). Mice born without the ability to make NT-3 have loss of proprioceptive and subsets of mechanoreceptive sensory neurons.

Neurotrophin-4[link]

Neurotrophin-4 (NT-4) is a neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase. It is also known as NT4, NT5, NTF4, and NT-4/5.^[12]

See also[link]

• Neurotrophic electrode

References[link]

External links[link]

• DevBio.com - 'Neurotrophin Receptors: The neurotrophin family consists of four members: nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4)' (April 4, 2003)
• Dr.Koop.com - 'New Clues to Neurological Diseases Discovered: Findings could lead to new treatments, two studies suggest', Steven Reinberg, HealthDay (July 5, 2006)
• Helsinki.fi - 'Neurotrophic factors'
• Neurotrophins at the US National Library of Medicine Medical Subject Headings (MeSH)
• [1] - Neurotrophin-3 image

This article incorporates text from the public domain Pfam and InterPro IPR002072

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Jack Herer and Dana Beal at the September 1989 Great Midwest Marijuana Harvest Fest in Madison, Wisconsin.

Jack Herer (June 18, 1939 – April 15, 2010), sometimes called the "Emperor of Hemp", was an American cannabis activist and the author of The Emperor Wears No Clothes, a book which has been used in efforts to decriminalize cannabis. Herer also founded and served as the director of the organization Help End Marijuana Prohibition (HEMP).^[1]

Biography[link]

A former Goldwater Republican, Herer was a pro-cannabis (marijuana) and hemp activist. He wrote two books, the aforementioned The Emperor Wears No Clothes and Grass. There has also been a documentary made about his life called, The Emperor of Hemp (cite?).

He believed that the cannabis plant should be decriminalized because it has been shown to be a renewable source of fuel, food, and medicine that can be grown in virtually any part of the world. He further asserts that the U.S. government deliberately hides the proof of this.

A specific strain of cannabis^[2] has been named after Jack Herer in honor of his work. This strain has won several awards, including the 7th High Times Cannabis Cup. Jack Herer was also inducted into the Counterculture Hall of Fame at the 16th Cannabis Cup in recognition of his first book.^[3]

Herer ran for United States President twice, in 1988 (1,949 votes) and 1992 (3,875 votes) as the Grassroots Party candidate.

Health problems and death[link]

In July 2000, Herer suffered a minor heart attack and a major stroke, resulting in difficulties speaking and moving the right side of his body.^[4] Herer mostly recovered, and claimed in May 2004 that treatment with the amanita muscaria, a psychoactive mushroom was the "secret".^[5]

On September 12, 2009 Herer suffered another heart attack while backstage at the Hempstalk Festival in Portland, Oregon.^[6] He spent nearly a month in critical condition in a Portland hospital, including several days in a medically induced coma. He was discharged to another facility on October 13, 2009. Paul Stanford of The Hemp and Cannabis Foundation said "He is waking up and gazing appropriately when someone is talking... but he is not really communicating in any way."^[7] He died aged 70 on April 15, 2010 in Eugene, Oregon, from complications related to the September 2009 heart attack.^[8][9] Herer was buried at the Eden Memorial Park Cemetery in Mission Hills, California.

Criticism[link]

European experts on hemp, like Dr. Hayo M.G. van der Werf author of the doctoral thesis Crop physiology of fibre hemp (1994) and Dr. Ivan Bûcsa, criticized Herer' for making unrealistic claims regarding the potential of hemp, for example:

- Herer claimed that hemp produces higher yields than other crops. Van der Werf argued that is simply wrong. Under most favorable growing conditions, other crops such as maize, sugar beet or potato produced similar dry matter yields. Fiber hemp is in no way exceptional.^[10] See also Hemp#Yield in modern agriculture

- Herer claimed that hemp hurds, which make up 60 to 80 % of the stem dry weight, contain 77 % cellulose. Van der Werf argued that is wrong. Cellulose content of hemp hurds has been found to vary between 32 and 38 % (Bedetti and Ciaralli 1976, van der Werf 1994). Possibly, Herer confused the hurds, which form the woody core of the hemp stem, with the bark, which forms the outer layer of the hemp stem. The bark contains the long bast fibers which are used in textile manufacturing.^[10]

- Herer claimed that hemp could be grown on 6 million hectares in the European Union, something that should have produced millions of tons of hemp fiber. The present production of hemp fiber in EU is only around 0.023 million ton/year.^[11] Dr. Ivan Bûcsa argue that it was a great exaggeration to expect millions of tons since it is not worth transporting unprocessed hemp more than 40-50 km even in bales.^[12]

Works[link]

Books

• 'The Emperor Wears No Clothes (1985, 1990) [online edition, text only]
• G.R.A.S.S.: Great Revolutionary American Standard System [with Al Emmanuel] (1973)

Articles

• "Cannabis Medicines Banned"
• "Hemp For Victory Coverup"

References[link]

External links[link]

• Official site
• Erowid Jack Herer Vault
• Jack Herer, Emperor of Hemp, Passes Away The 420 Times
• Emperor Of Hemp full Documentary

Rick Simpson is an American set decorator. He won an Academy Award and was nominated for another in the category Best Art Direction.^[1]

Awards[link]

Simpson won an Academy Award for Best Art Direction and was nominated for another:

Won

• Dick Tracy (1990)^[2]

Nominated

• 2010 (1984)

Selected filmography[link]

• Silent Movie (1976)
• Capricorn One (1977)
• Coma (1978)
• The Champ (1979)
• Personal Best (1982)
• Something Wicked This Way Comes (1983)
• The Star Chamber (1983)
• 2010 (1984)
• Johnny Dangerously (1984)
• Project X (1987)
• Tequila Sunrise (1988)
• Dick Tracy (1990)
• Predator 2 (1990)
• City Slickers (1991)
• Born Yesterday (1993)
• What's Love Got to Do with It (1993)
• The Pelican Brief (1993)
• Boys on the Side (1995)
• Casino (1995)
• Sgt. Bilko (1996)
• Bulworth (1998)
• Armageddon (1998)
• Little Nicky (2000)
• Rush Hour 2 (2001)
• The Hunted (2003)
• 2 Fast 2 Furious (2003)
• Rules of Engagement (2000)
• The Black Dahlia (2006)

References[link]

External links[link]

• Rick Simpson at the Internet Movie Database
• Rick Simpson at AllRovi

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