presentación nucleo uct 2012 ii
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Plantas medicinales y terapias alternativas en Alzheimer. Una tierra desconocida
Laboratorio de Fisiología de la Reproducción
Jorge Parodijparodi@uct.cl
http://www.alz.org/alzheimers_disease_alternative_treatments.asp
Caprylic acid and coconut oil ConcernsCoenzyme Q10Coral calciumGinkgo bilobaHuperzine AOmega-3 fatty acidsPhosphatidylserineTramiprosate
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
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
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
Palmer 2002 Trends in Phar
Benilova et al 2012 Nature Neuroscience
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
Parodi et al (2010) JBC
Savonenko et al (2005) Neurobiology of Disease
Dinamarca et al (2006) Molecular Psychiatry
Inestrosa et al (2011) Translation Psychiatry
Montesinos et al (2012) in report
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
C
BA
D
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
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
Ẳ
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
-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
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
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
*
AgradecimientosDr. Luis AguayoDr. Nibaldo InestrosaFernando SepulvedaDavid Ormeño
Laboratorio de Fisiología de la ReproducciónFelipeGuillermoDaniela
ColaboradoresDr. Alexander OrtloffMsC Patricio Peña
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