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Selegiline as immunostimulant - a novel mechanism of action?
Muller T, Kuhn W, Kruger R, Przuntek H
Department of Neurology,
St. Josef-Hospital, University of Bochum,
Federal Republic of Germany.
Nature, 1996 Feb, 379: 6567, 733-6
ABSTRACT
In clinical studies the MAO-B inhibitor
selegiline appears to slow the progression of neurological deficits in
Parkinson's disease (PD) and the cognitive decline in Alzheimer's disease
(AD). The mechanisms of action remain unclear. Several lines of evidence
indicate an immune-mediated pathophysiology of PD and AD. According to
animal trials, selegiline increases the survival rate of immune suppressed
mice. Stimulation of the immune response to bacterial or viral infection or
in chronic inflammatory processes in managed by an increased synthesis of
the cytokines interleukin-1 beta (IL-1 beta) and subsequent interleukin-6
(IL-6). Outcome of viral or bacterial infections in the brain highly
correlates with levels of the cytotoxic cytokine tumor-necrosis-factor-alpha
(TNF). The aim of our study was to characterize the influence of selegiline
on the biosynthesis of IL-1 beta, IL-6 and TNF in human peripheral blood
mononuclear cells (PBMC) from healthy blood donors. After isolation and
washing PBMC were cultured without and with selegiline in three different
concentrations (0.01 mumol/l, 0.001 mumol/l, 0.0001 mumol/l) in a humidified
atmosphere (7% CO2). Then cultures were centrifuged and supernatants were
collected for IL-1 beta, IL-6 and TNF ELISA-assays. Treatment of cultured
PBMC with various concentrations induced an increased synthesis of IL-1 beta
(ANOVA F = 9.703, p = 0.0007), IL-6 (ANOVA F = 20.648, p = 0.0001) and a
reduced production of TNF (ANOVA F = 3.770, p = 0.040). These results
indicate, that the influence of selegiline on the cytokine biosynthesis may
also contribute to its putative neuroprotective properties.
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Deprenyl in
the treatment of Alzheimer's disease
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Deprenyl MAO-B inhibitors in the treatment of Alzheimer's disease
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Deprenyl for Alzheimer's disease
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Deprenyl stimulates biosynthesis of cytokines interleukin-1 &
6
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Deprenyl and
age-related decline of the striatal dopaminergic system
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Deprenyl
improves memory in amnesic Alzheimer's patients
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Deprenyl
treatment of behavioral symptoms of Alzheimer's disease
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Deprenyl
increases life span in Parkinson's
patients
- Deprenyl
possible mechanisms of action in Parkinson's disease
- Deprenyl
effect on arm movement in early Parkinson's
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Deprenyl
effect
on cognitive functions in early Parkinson's
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Deprenyl
possible mechanisms of action
in Parkinson's
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Deprenyl
depression
in Parkinson's disease
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Deprenyl
improves visuo-motor control in
early Parkinsonism
-
Deprenyl
management of early Parkinson's disease
-
Deprenyl
delays the onset of
disability in Parkinsonian patients
-
Deprenyl
and tocopherol antioxidative therapy of
Parkinsonism
- Deprenyl
treatment and death of nigral neurons in
Parkinson's disease.
- Deprenyl
rationale for deprenyl medication in
Parkinson's disease
-
Deprenyl
and levodopa in Parkinson's disease
-
Deprenyl
is an MAO-B inhibitor
-
Deprenyl
facilitates neuronal growth without
inhibiting monoamine oxidase
-
Deprenyl
pharmacology
-
Deprenyl
biochemical actions
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Deprenyl
effect
of MAO-B inhibitors on MPP+ toxicity
-
Deprenyl
the
history of its development
-
Deprenyl
protects neurons against neurotoxins
-
Deprenyl
in neurodegenerative disorders
-
Deprenyl
enhances the release of dopamine
- Deprenyl
plus L-phenylalanine in the
treatment of depression
- Deprenyl
in the treatment-resistant of older depressive patients
- Deprenyl
effects in atypical depressives
-
Deprenyl
up-regulates superoxide dismutase and catalase
- Deprenyl immunostimulant
- Deprenyl
pharmacology
- Deprenyl
effect on rat longevity and sexual
acitivity
- Deprenyl
effects of experimental
cocaine administration
- Deprenyl
effects on longevity in
animals
- Deprenyl
effects on subjective ratings of
cocaine-induced euphoria
- Deprenyl
increases the life span in Fischer
rats
- Deprenyl
effects on short term memory in
young and aged dogs
- Deprenyl
the
facilitation of dopaminergic activity in the aged brain
- Deprenyl
fluoxetine (Prozac) and deprenyl
- Deprenyl
improves
cardiac sympathetic terminal function in heart failure
- Deprenyl
effect
on dopamine concentration in the striatum of a primate
- Deprenyl
a review of the pharmacology
- Deprenyl
restores IGF-1 levels to young
levels
- Deprenyl
prolongs life
in elderly dogs
-
Deprenyl past, present, and
future
- Deprenyl
relevance
to humans
- Deprenyl
responses of forebrain neurons to
deprenyl
- Deprenyl
protects
neurons from glutamate toxicity
- Deprenyl
nitric oxide production and
dilation of cerebral blood vessels
- Deprenyl
modulates the decline of the
striatal dopaminergic system
- Deprenyl
inhibits tumor growth in rats with
mammary tumors
- Deprenyl
a catecholaminergic activity
enhancer in the brain
- Deprenyl
releases coupling in the catecholaminergic neurons
- Deprenyl
clinical potential in neurologic and psychiatric disorders
- Deprenyl
protects human dopaminergic neuroblastoma cells
- Deprenyl
nitric oxide production and
dilation of cerebral blood vessels
- Deprenyl
assessing the
effects of deprenyl on longevity of animals
- Deprenyl
effects on cocaine-induced euphoria
- Deprenyl
effects on
response to experimental cocaine administration
- Deprenyl
Are metabolites of
deprenyl useful or harmful?
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Deprenyl
is devoid of amphetamine-like
effects
- Deprenyl treated rats lived beyond the known
maximum lifespan
-
Deprenyl
stimulates biosynthesis of cytokines interleukin-1 & 6
-
Deprenyl
pharmacological basis
of the beneficial effects
-
Deprenyl
modulates the decline of the dopamineric system
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