NERVE GROWTH FACTORS AND NEUROTROPHINS

1. DR NILESH KATE
MBBS,MD
PROFESSOR
ESIC MEDICAL COLLEGE, GULBARGA.
DEPT. OF PHYSIOLOGY
NERVE GROWTH
FACTORS &
NEUROTROPHINS
& CYTOKINES.

2. OBJECTIVES.
 Neurotrophins
 Nerve growth factors.
 Other growth promoting factors.
 Cytokines.

3. NEUROTROPHINS.
 Proteins which provide trophic support to
the neurons.
 Promote nerve growth & survival.
Play role in NEURONAL PLASTICITY.
Tuesday, December 6, 2022

4. NEUROTROPHINS.
 A member of a family of small secreted
protein known as Neurotrophins that
function as a Signaling molecule.
Tuesday, December 6, 2022

6. PRODUCTION
Muscles
Glands
Astrocytes
Tuesday, December 6, 2022

7. TRANSPORT
Produced by
various structure
innervated by
neuron
Bind to receptor
at nerve ending.
Internalize by
Endocytosis.
Transported by
retrograde
axoplasmic flow
In cell body increase production
of proteins associated with
neuronal development, growth &
survival
Tuesday, December 6, 2022

8. NEUROTROPHIN RECEPTORS
 Each neurotrophin can signal through two
different types of cell surface receptor
 Trk receptor -Tyrosine kinases
 p75 neurotrophin receptor (p75NTR).
 Transmembrane receptor, also known as TNFRSF16.
 a member of the tumour necrosis factor receptor (TNFR) death-
receptor family.

9. NEUROTROPHIN RECEPTORS
 The ratio of receptors is
important in dictating
the numbers of
surviving cells.
 Interactions between
p75 and Trk receptors
provide greater
discrimination between
different neurotrophins.

10. NEUROTROPHINS
It includes.
 Nerve growth factors,
 Brain derived neurotrophic factors.
 Glial derived neurotrophic factors.
 Neurotrophin 3
 Neurotrophin 4/5.
Tuesday, December 6, 2022

11. NERVE GROWTH FACTORS.
 First neurotrophins recognized.
 Promotes growth of sympathetic nerves and
sensory nerves.
Tuesday, December 6, 2022

12. HISTORY.
 1986.
 Rita Levi-Montalcini
& stanley cohen
Idenfied NGF.
Tuesday, December 6, 2022

13. RITA LEVI-MONTALCINI
& STANLEY COHEN
 They demonstrated that number of nerve cells
produced in the embryo could be influenced by
antigen (NGF) obtained from mouse tumour cell
culture.
 Picked up by axon terminal of growing motor
neurons
 Prevents apoptosis.
Tuesday, December 6, 2022

14. NERVE GROWTH
FACTOR….WHAT IS IT?
 These are naturally occurring essential biological
mediators that promotes cell growth, differentiation,
survival and function in specific nerve cell population
 A proteins that causes developing cells to grow by
stimulating surrounding nerve tissue.
Tuesday, December 6, 2022

15. IN FETUS.
 Embryonic development of sensory neurons
and sympathetic ganglia (NGF &
Neurotrophin -3)
Tuesday, December 6, 2022

16. STRUCTURE.
 Made up of 2α, 2β and 2γ subunits.
 α subunits – trypsin like activity
 β subunit similar to insulin.
 γ subunit are serine proteases.
Tuesday, December 6, 2022

17. RECEPTORS & ACTION
 Mainly Trk A
(Tyrosine kinase
activity A)
 Also present in brain
& responsible for
growth & maintenance
of of cholinergic
neurons in basal
forebrain & striatum.
Tuesday, December 6, 2022

18. BRAIN DERIVED
NEUROTROPHIC FACTORS.
 Growth promoting
role in peripheral
sensory nerves.
 Receptor is Trk B
Tuesday, December 6, 2022

19. NEUROTROPHIN 3
 Plays growth
promoting role in
cutaneous
mechanoceptors.
 Receptors are Trk-C &
Trk-A & Trk-B
Tuesday, December 6, 2022

20. NEUROTROPHIN 4/5.
 Receptor is Trk-B
Tuesday, December 6, 2022

21. OTHER GROWTH PROMOTING FACTORS.
(LIFT-PC)
 Leukaemia inhibitory factors
 Insulin like growth factors.
 Fibroblast growth factors
 Transforming growth factors.
 Platelet derived growth factors.
 Ciliary neurotrophic factors.
Tuesday, December 6, 2022

22. CILIARY NEUROTROPHIC
FACTORS.
 Produced by Schwann cells and Astrocytes
 Plays a growth promoting role in lesioned &
embryonic spinal cord neurons.
Tuesday, December 6, 2022

23. FUNCTIONS.
 Neuronal Proliferation.
 Proliferation of pancreatic beta cells.
 Regulation of the immune system.
Tuesday, December 6, 2022

24. CLINICAL SIGNIFICANCE
 NGF prevents or reduces neuronal degeneration
in neurodegerative diseases .
 NGF promotes peripheral nerve regeneration in rats.
 The expression of NGF is increased in inflammatory diseases
where it suppresses inflammation.
 NGF appears to promote myelin repair. Hence NGF may be
useful for the treatment of multiple sclerosis .
 NGF could also be involved in various psychiatric disorders ,
such as dementia, depression, schizophrenia, autism, Rett
syndrome, anorexia nervosa, and bulimia nervosa
Tuesday, December 6, 2022

25. CYTOKINES.
 Small protein molecules which acts like a
hormone to regulate immune response.
Tuesday, December 6, 2022

26. PRODUCTION.
 Produced not only by lymphocytes &
macrophages but also by endothelial cells,
neuroglial cells
Tuesday, December 6, 2022

27. TYPES.
 Interleukins (IL-1 to
13)
 Other cytokines
 Chemokines.
Tuesday, December 6, 2022

28. MECHANISM OF ACTION.
 Local effects
 Systemic effects.
Tuesday, December 6, 2022

29. LOCAL EFFECTS.
 Act in autocrine or
paracrine manner
through specific
receptors.
 Superfamily includes
receptors of
 Cytokines
 Haemopoietic growth
factor
 Prolactin
 Growth hormone
Tuesday, December 6, 2022

30. SYSTEMIC EFFECTS.
 CNS – causes fever, slow wave sleep, secretion of
CRH.
 Metabolic effect – stimulate hepatic protein
synthesis, causes lactic acidosis.
 Haematological effects – increases neutrophils,
colony stimulating factors
 Vascular system – stimulate leucocyte adherence
to vessel wall, prostaglandin synthesis, platelet
activating factor & increases capillary permeability.
Tuesday, December 6, 2022

31. OBJECTIVES……..
 Neurotrophins
 Nerve growth factors.
 Other growth promoting factors.
 Cytokines.

32. THANK YOU