Presentación nucleo uct 2012 ii

31
Plantas medicinales y terapias alternativas en Alzheimer. Una tierra desconocida oratorio de Fisiología de la Reproducc Jorge Parodi [email protected]

Transcript of Presentación nucleo uct 2012 ii

Page 1: Presentación nucleo uct 2012 ii

Plantas medicinales y terapias alternativas en Alzheimer. Una tierra desconocida

Laboratorio de Fisiología de la Reproducción

Jorge [email protected]

Page 2: Presentación nucleo uct 2012 ii
Page 3: Presentación nucleo uct 2012 ii
Page 4: Presentación nucleo uct 2012 ii
Page 5: Presentación nucleo uct 2012 ii

http://www.alz.org/alzheimers_disease_alternative_treatments.asp

Caprylic acid and coconut oil ConcernsCoenzyme Q10Coral calciumGinkgo bilobaHuperzine AOmega-3 fatty acidsPhosphatidylserineTramiprosate

Page 6: Presentación nucleo uct 2012 ii

Conclusion Compared with placebo, the use of G biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment.

Snitz et al 2009 JAMA

Test Placebo Ginko

Memory 0,15 0,14

Executive test 3,27 3,47

Page 7: Presentación nucleo uct 2012 ii

Date of download: 7/14/2012Copyright © 2012 American Medical Association.

All rights reserved.

From: Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease:  A Randomized Trial

JAMA. 2010;304(17):1903-1911. doi:10.1001/jama.2010.1510

Page 8: Presentación nucleo uct 2012 ii

Danitz and Parsons 2008 IJNP

Donepezil and Memantine for Moderate-to-Severe Alzheimer's Disease

Conclusions In patients with moderate or severe Alzheimer's disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months JAMA 2012

Page 9: Presentación nucleo uct 2012 ii

Palmer 2002 Trends in Phar

Page 10: Presentación nucleo uct 2012 ii

Benilova et al 2012 Nature Neuroscience

Page 11: Presentación nucleo uct 2012 ii
Page 12: Presentación nucleo uct 2012 ii

Agregados Ab1-40 se localizan en regiones sinápticas

Ab – DAC (1:2)24 horas0.5 mM

MAP1B – Cy3 A

Ab - DAC B

SV2 – Cy5 C G

H

10 mm

D

H

G

Page 13: Presentación nucleo uct 2012 ii

Parodi et al (2010) JBC

Page 14: Presentación nucleo uct 2012 ii
Page 15: Presentación nucleo uct 2012 ii
Page 16: Presentación nucleo uct 2012 ii

Savonenko et al (2005) Neurobiology of Disease

Page 17: Presentación nucleo uct 2012 ii

Dinamarca et al (2006) Molecular Psychiatry

Page 18: Presentación nucleo uct 2012 ii

Inestrosa et al (2011) Translation Psychiatry

Page 19: Presentación nucleo uct 2012 ii

Montesinos et al (2012) in report

Page 20: Presentación nucleo uct 2012 ii

Modeling

0 50 100 150 200

0,0

0,2

0,4

0,6

0,8

1,0

1,2

Tiempo (min)

Tu

rbim

etri

a (D

.O. 4

05 n

m)

Control 5 mM Etanol 10 mM Etanol 50 mM EtanolA B

C D E

Ormeño et al (2012) in review

Page 21: Presentación nucleo uct 2012 ii
Page 22: Presentación nucleo uct 2012 ii

C

BA

D

Page 23: Presentación nucleo uct 2012 ii

A

ASP-23

LYS-28

B

ASP-23

LYS-28

2.7Ẳ

ASP-23

LYS-28C

12.7Ẳ

D

ASP-23

LYS-28

6.3Ẳ

Page 24: Presentación nucleo uct 2012 ii

0,0 0,5 1,0 1,5 2,0 2,50

2

4

6

8

10

12

Time (ns)

Control Ethanol 10 %

A

0,0 0,5 1,0 1,5 2,0 2,5

0

5

10

15

20

25 Control Ethanol 1%

Dev

iation (R

MSD

) Time (ns)

B

Page 25: Presentación nucleo uct 2012 ii

Control

Trata

das 1 5 10 25 50 100

0,0

0,5

1,0

1,5

2,0

2,5

*

*

**

Etanol (mM)

Agregados amilodes

Fre

cuen

cia

(Hz)

Act

ivid

ad S

ináp

tica

Esp

on

tán

ea

Control

Agregados A 0.5 M (24 h)

Agregados A 0.5 M + 10 mM Etanol (24 h)

Agregados A 0.5 M + 50 mM Etanol (24 h)

50 mM Etanol (24 h)

0.2 s 20 p

A

0.2 s 20 p

A

0.2 s 20 p

A0.2 s 20

pA

0.2 s 20 p

A

Sv2

Control

Aaggregates 0.5 M

Aβ aggregates 5 M

Aβ aggregates 10 M

10 mM etanol

50 mM etanol

Aaggregates 0.5 M

Ormeño et al (2012) in review

Page 26: Presentación nucleo uct 2012 ii
Page 27: Presentación nucleo uct 2012 ii

-6 -5 -4 -3 -2 -1 0 10,0

0,5

1,0

1,5

Num

ber

of events

Amplitude (nA)

Control Gramicidin Amphotericin B Aggregate

A B C

-200 -150 -100 -50 0 50 100

-8

-6

-4

-2

0

2

4

6

8

nA

mV

Aggregate Gramicidin Amphotericin Control

Contro

l

Gramicidin

Amph

otericin B

Aggr

egates

0

-200

-400

-600

-800

-1000

**

Mem

bra

ne c

onducta

nces (nS

)

*

Parodi et al (2012) in review

Page 28: Presentación nucleo uct 2012 ii

B

C

A

D

+ 20 mV0 mV

Control

Aggregate

High Ca2+

NR

High Ca2+

NR

-100 mV

+ 20 mV0 mV

-100 mV

100 nA250 ms

4 min

200

nA

Rabbit serum

15 min Aggregate

0 min 15 min

NR

0

50

100

150

200

250

300

Aggregate

High Ca2+NR

*

*

Curr

ent a

mplit

ude

(% o

f co

ntr

ol a

t +20

mV)

*

NR High Ca2+

0

50

100

150

200

15 min Aggregate15 min

*

Curr

ent am

plit

ude

(% o

f co

ntr

ol ) NR

0 min

Page 29: Presentación nucleo uct 2012 ii

20

0 n

A

60 s

100 μM ATP0 min 15 min

15 min AggregateNR

0

20

40

60

80

100

120

15 min Aggregate15 min

Cu

rre

nt

(% o

f c

on

tro

l)

0 min

*

Page 30: Presentación nucleo uct 2012 ii
Page 31: Presentación nucleo uct 2012 ii

AgradecimientosDr. Luis AguayoDr. Nibaldo InestrosaFernando SepulvedaDavid Ormeño

Laboratorio de Fisiología de la ReproducciónFelipeGuillermoDaniela

ColaboradoresDr. Alexander OrtloffMsC Patricio Peña