神经生物学课件神经营养因子

The life cycles of NTF
Biosynthesis ：synthesized mainly in the
nerval cell body, including neuron and glia.
Storage： stored in the large dense core
vesicles, and was transported to nerve terminal or extended dendrite.
Neurite (神经突起)
The effect of NGF on cultured spinal neurons
(Levi-Montalcini R. 1987. Science 237:1157)
Neuritic branch is described axon and dendrite. Especially, it is available for growing neurite which did not assured axon or dendrite.
Coupled to JAK, R-PTKs Coupled to JAK
G protein-coupled receptors CC1-CC8R CXC1-CXC4R Cx3C1R
Neurotrophins
Neurotrophins are small proteins. They produce their physiologic effects by means of the Trk receptor family.
Family menbers：NGF、BDNF、NT-3、NT-4/5。
Effections
surviv源自文库l of neurons
Preventing to death of neurons
neurogenesis Promote axons and dendrites growth.
neurite
Autocrine transmission
Anterograde tramsmission
Paracrine transmission
Retograde transmission
NTF与神经肽的区别
Molecular weight
NTF
large，>14kDa
NP
small, < kDa
Synthesis NTF is produced in cell body.
IL-1, IL-2, IL-3, IL-5,TNF, TNF TGF family TGF
Receptors Trk （R-PTKs） TrkA 、TrkB、TrkC1 Coupled to Ret GFR1、GFR2、 nu-known Coupled to Janus kinase（JAK ） GP130、CNTFR、LIFR Eph (R-PTKs) ErbB (R-PTKs)
Promote neurite of axons and dendrites.
Anabolism Enhance the size of neuronal body.
differentiation Proteins are necessary for neuronal differentiation.
<1kDa
produced at the terminal
Synaptic vesicles
Release breakdown Signaling
Action
active-dependent synthesis. depolarization.
Low-frequency stimulation depolarization.
The term of Neurotrophic factor
The term Neurotrophic Factor refers to any molecule that affects the nerves system by influencing the growth, differentiation, or cell cycles of neurons or glia.
Signaling to many of the biologic effects
Actions
retograde, anterograde, autocrine,
paracrine transmission.
NP is produced in cell body
large densecored vesicles
protease hydrolyzation, enshroud by incativationreceptor
reuptake, re-use,
the binding to Trk receptor lead to many of the biologic effects
The binding G-protein couple receptor and the second messenger lead to the biologic effects.
retograde, anterograde, autocrine, anterograde,
autocrine,
paracrine transmission.
paracrine transmission. acting
as ‘quick’ transmitter.
分 类
Neurotrophic Factors Neurotrophins
The difference between of NTFs and Neuropeptides:
1) NTFs are large molecular proteins, but neuropeptides are the small molecular proteins (< 30-40 peptides).
R-PTKs
IL-IR coupled to PS/TK, R-PTK Coupled to JAK, Related to p753 R-PS/TRs
Other cytokines interferons (IFN, , ), m-CSF, gm-CSF
Chemokines CC chemokines (IL-8) CXC chemokines (MIP, MCP) CX3C chemokines (neurotactin)
NGF、BDNF、NT-3、NT-4 GDNF family
GDNF 、neurturin、persephin CNTF family
CNTF、LIF、IL-6 Ephrins EGF family
EGF, TGF, neuregulns2 Other growth factors
Insulin, IGF, FGF, PDGF interleukins and related cytokines
electric stimulation, hyperpotassium caused
depolarization.
protease hydrolyzation
The binding G-protein couple receptor and the second messenger lead to the biologic effects.
Breakdown： Broken down by membrane peptidases BDNF was detained by functional-inactive receptor and then its dispersion was baffled. Simultaneity the persistence-action window was also restricted.
Chap 16 Neurotrophic Factor 神经营养因子
History
It was known that extracellular signals can promote the growth and differentiation of nerve cells in more than half a century ago.
The partnership of activation-synthesis results to NTFs high-complicated forms in intercellular information of neurons and glia.
Modes of intercellular communication subserved by NTF
anterograde, autocrine, paracrine transmission.
NTF与神经递质的区别
NTF
Classical transmitters
Molecular weight
Synthesis
Storage
Large, >14kDa
producted in cell body large densecored vesicles
Storage large densecored vesicles
Release
active-dependent synthesis. depolarization.
Breakdown
protease hydrolyzation, detained by inactivation-receptor
The binding to Trk receptor lead
Neurotrophic factor (NTF) influences the growth, differentiation and survival of neurons during development.
NTFs are also re-activated in adulthood in tissue renewal or regeneration.
Nerve growth factor (NGF) was first discovered by Bueker in 1948.
Rita Levi-Montalcini and Victor Hamburger demonstrated NGF is necessary for sympathetic and sensory neurons NGF to keep their survival.
2) Difference molecular signaling pathway.
NTF
NP
The difference between of NTFs and nonpeptides:
NTFs are distinguished from many nonpeptide molecules, including steroid hormones, retinoic acid and neurotransmitters, that also can influence the growth and integrity of the nervous system.
The signaling failure of NTF may underlie neurodegenerative disorders such as Alzheimer disease (AD), Parkinson disease (PD), huntington disease (HD) and amyotrophic lateral sclerosis (ALS).
The life cycles of NTF
Release： Some NTFs, including BDNF and GDNF, were produced from immediate-early genes, therefore, their release was depend on active-dependent synthesis. The others were depend on their depolarization.