Bee venom contain many components like bee venom phospholipase A2 and apamin etc bee venom phospholipase A2 decrease the neuroinflammation in parkinson's disease helpful to treat PD.

1. Bee Venom Phospholipase A2, a Novel
Foxp3+
Regulatory T Cell Inducer, Protects
Dopaminergic Neurons by Modulating
Neuroinflammatory Responses in a Mouse Model of
Parkinson’s Disease
Presented by:-
SAKEEL AHMED
NIPERA1820PC01
Dept. Of Pharmacology & Toxicology
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2. FLOW OF SEMINAR
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CHUNG, E. S., LEE, G., LEE, C., YE, M., CHUNG, H.-S., KIM, H., SUNG-JOO, S. B., HWANG, D.-S. & BAE, H. 2015. Bee venom phospholipase
A2, a novel Foxp3+ regulatory T cell inducer, protects dopaminergic neurons by modulating neuroinflammatory responses in a mouse model of
Parkinson’s disease. The Journal of Immunology, 195, 4853-4860.

3. ∗ Parkinson disease is the progressive neurodegenerative
disorder in which the predominantly dopaminergic
neuron in the substantia nigra pars compacta .
∗ PD characterized by the rigidity, postural instability ,
tremor & dyskinesia .
∗ In PD there are mutation in the SNCA, LRRK2 & PARK8.
∗ Mutation in these gene leads to the aggregation of α-
synuclein.
PARKINSON’S DISEASE (PD)
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4. Bee Venom Phospholipase A2
(bvPLA2)
∗ PLA2 catalyzes the hydrolysis of the fatty acyl bond of
phospholipids to liberate free fatty acids and lysophospholipids.
This enzyme, naturally found in the venom of various species,
including reptiles and insects.
∗ bvPLA2 induces Th2 response, which may have contributed to
the suppression in the experimental model of PD.
∗ Additionally, an enhanced level of PGE2 by bvPLA2 treatment
may promote the Th2 response.
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CHUNG, E. S., LEE, G., LEE, C., YE, M., CHUNG, H.-S., KIM, H., SUNG-JOO, S. B., HWANG, D.-S. & BAE, H. 2015. Bee venom phospholipase
A2, a novel Foxp3+ regulatory T cell inducer, protects dopaminergic neurons by modulating neuroinflammatory responses in a mouse model of
Parkinson’s disease. The Journal of Immunology, 195, 4853-4860.

5. HYPOTHESIS
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Inhibit Microglial
activation
Inhibit CD4+ T cells
infiltration

6. ∗ Animals:-
∗ They were conducted on 7- to 8-wk-old male C57BL/6
mice (21–22 g).
∗ Foxp3 EGFP/DTR C57BL/6-transgenic mice.
∗ Foxp3 EGFP C57BL/6 mice.
∗ CD206 -/- mice.
∗ All mice were maintained under pathogen-free
conditions with air conditioning, a 12/12-h light/dark
cycle, and food provided ad libitum.
OBJECTIVES
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CHUNG, E. S., LEE, G., LEE, C., YE, M., CHUNG, H.-S., KIM, H., SUNG-JOO, S. B., HWANG, D.-S. & BAE, H. 2015. Bee venom phospholipase
A2, a novel Foxp3+ regulatory T cell inducer, protects dopaminergic neurons by modulating neuroinflammatory responses in a mouse model of
Parkinson’s disease. The Journal of Immunology, 195, 4853-4860.

7. 7
bvPLA2 is the active molecule in BV that increases
Tregs.
***p , 0.001

8. Tregs Expension
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*p , 0.05, **p , 0.01, ***p , 0.001, n = 5–7

9. Suppressive
ability of bvPLA2-treated Tregs
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e670

10. bvPLA2 prevents MPTP-induced neurotoxicity in the SN.
MPTP-injected mice were treated with bvPLA2 or PBS for 6 d
starting at 12 h after the last MPTP injection.
n= 5-9 10

11. Treatment of MPTP-injected mice with bvPLA2
prevents DA neuronal death accompanied by
Microglial deactivation
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C M M+P

12. Infiltration of CD4 T cells in the SN
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13. Treg depletion prevents the neuroprotective effects of
bvPLA2 in MPTP-injected mice.
n= 4-8 13

14. 14
bvPLA2 binding on CD206+ DCs is required for Treg
differentiation
CHUNG, E. S., LEE, G., LEE, C., YE, M., CHUNG, H.-S., KIM, H., SUNG-JOO, S. B., HWANG, D.-S. & BAE, H. 2015. Bee venom phospholipase
A2, a novel Foxp3+ regulatory T cell inducer, protects dopaminergic neurons by modulating neuroinflammatory responses in a mouse model of
Parkinson’s disease. The Journal of Immunology, 195, 4853-4860.

15. Surface plasmon resonance assay
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16. SPR & Cell specificity
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17. 17

18. 18
PGE2 secreted by CD206+ DCs contributes to the
induction of Tregs via the EP2 receptor.

19. 19

20. 20

21. ∗ They first demonstrated that bvPLA2 is the major BV
compound capable of inducing Treg expansion without altering
the total composition of the other cell types in vivo and in
vitro.
∗ They showed that bvPLA2 has neuroprotective effects by
suppressing microglial activation and reducing the infiltrating
CD4+ T cells in the MPTP induced mouse model of PD.
∗ Neuroprotective effects, bvPLA2directly binds to the mannose
receptor (CD206) on DCs, and this binding induces the release
of PGE2, which promotes Treg induction in CD4 T cells.
DISCUSSION
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CHUNG, E. S., LEE, G., LEE, C., YE, M., CHUNG, H.-S., KIM, H., SUNG-JOO, S. B., HWANG, D.-S. & BAE, H. 2015. Bee venom phospholipase
A2, a novel Foxp3+ regulatory T cell inducer, protects dopaminergic neurons by modulating neuroinflammatory responses in a mouse model of
Parkinson’s disease. The Journal of Immunology, 195, 4853-4860.

22. ∗ Their findings demonstrate a novel effect of bvPLA2: the
mediation of immune suppression through controlling PGE2
secretion by CD206+ DCs. PGE2 released by bvPLA2-stimulated
DCs acts on the EP2 receptor in CD4+ T cells, and this binding
leads to the upregulation of Foxp3 expression. bvPLA2 may
thus be a potential candidate for treating PD and other
disorders associated with neuroinflammation.
CONCLUSION
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CHUNG, E. S., LEE, G., LEE, C., YE, M., CHUNG, H.-S., KIM, H., SUNG-JOO, S. B., HWANG, D.-S. & BAE, H. 2015. Bee venom phospholipase
A2, a novel Foxp3+ regulatory T cell inducer, protects dopaminergic neurons by modulating neuroinflammatory responses in a mouse model of
Parkinson’s disease. The Journal of Immunology, 195, 4853-4860.