1. Plantas medicinales y terapias alternativas en
Alzheimer. Una tierra desconocida
Laboratorio de Fisiología de la Reproducción
Jorge Parodi
jparodi@uct.cl

5. http://www.alz.org/alzheimers_disease_alternative_treatm
ents.asp
Caprylic acid and coconut oil
Concerns
Coenzyme Q10
Coral calcium
Ginkgo biloba
Huperzine A
Omega-3 fatty acids
Phosphatidylserine
Tramiprosate

6. Test Placebo Ginko
Memory 0,15 0,14
Executive test 3,27 3,47
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

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

8. 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
Danitz and Parsons 2008 IJNP

9. Palmer 2002 Trends in Phar

10. Benilova et al 2012 Nature Neuroscience

12. Agregados A 1-40 se localizan en regiones sinápticas
MAP1B – Cy3 A D
A – DAC (1:2)
24 horas H
0.5 M
A - DAC B
G
SV2 – Cy5 C G
H
10 m

13. Parodi et al (2010) JBC

16. Savonenko et al (2005) Neurobiology of Disease

17. Dinamarca et al (2006) Molecular Psychiatry

18. Inestrosa et al (2011) Translation Psychiatry

19. Montesinos et al (2012) in report

20. 1,2
Control
5 mM Etanol
1,0 10 mM Etanol
A B 50 mM Etanol
(D.O. 405 nm)
Turbimetria
0,8
0,6
0,4
0,2
0,0
0 50 100 150 200
Tiempo (min)
C D Modeling E
Ormeño et al (2012) in review

22. A B
C D

23. A B
LYS-28 LYS-28
2.7Ẳ
ASP-23
ASP-23
C LYS-28 D
12.7Ẳ
LYS-28
6.3Ẳ
ASP-23
ASP-23

24. A B
12 25
Control Control
Ethanol 10 % Ethanol 1%
10 20
Deviation (RMSD)
8 15
Ẳ
6
10
4
5
2
0
0
0,0 0,5 1,0 1,5 2,0 2,5 0,0 0,5 1,0 1,5 2,0 2,5
Time (ns) Time (ns)

25. 2,5
Actividad Sináptica Espontánea
Agregados amilodes
2,0
Frecuencia (Hz)
1,5
*
1,0
*
Control
*
0,5
20 pA
*
0.2 s
0,0
Agregados A 0.5 M (24 h)
10
25
50
0
1
5
as
ol
10
tr
ad
on
20 pA
at
Etanol (mM)
C
Tr
0.2 s
Agregados A 0.5 M + 10 mM Etanol (24 h)
20 pA
0.2 s
Agregados A 0.5 M + 50 mM Etanol (24 h)
Sv2
20 pA
0.2 s
50 mM Etanol (24 h)
20 pA
0.2 s
A aggregates 0.5 M
Ormeño et al (2012) in review

27. A B C
8
1,5 -1000 Aggregate
Membrane conductances (nS)
Control
Gramicidin Gramicidin 6
Number of events
Amphotericin B Amphotericin
Aggregate -800
* Control 4
1,0 *
-600 * 2
mV
0
-400 -200 -150 -100 -50 0 50 100
0,5
-2
-200
-4
0,0 0 -6
-6 -5 -4 -3 -2 -1 0 1
s
ol
in
B
te
nA
tr
id
in
Amplitude (nA)
ga
on
ic
ic
-8
re
m
er
C
ra
gg
ot
G
ph
A
m
A
Parodi et al (2012) in review

28. A B
Control
300
(% of control at 20 mV)
High Ca2+
*
Current amplitude
NR 250
+ 20 mV
0 mV
+
200
-100 mV *
150 *
Aggregate
100 nA
250 ms 100
High Ca2+
NR 50
+ 20 mV
0 mV 0
-100 mV NR High Ca2+ NR High Ca2+
Aggregate
200
C D
Current amplitude
*
(% of control )
NR 15 min Aggregate 150 NR
0 min 15 min
Rabbit serum
100
50
200 nA
0
4 min
0 min 15 min 15 min Aggregate

29. NR 15 min Aggregate
0 min 15 min
100 μM ATP
120
Current (% of control)
100
80
60
40
*
200 nA
20
0
60 s 0 min 15 min 15 min Aggregate

31. Agradecimientos
Dr. Luis Aguayo
Dr. Nibaldo Inestrosa
Fernando Sepulveda
David Ormeño
Laboratorio de Fisiología de la Reproducción
Felipe
Guillermo
Daniela
Colaboradores
Dr. Alexander Ortloff
MsC Patricio Peña