Jaarboek no. 89. 2010/2011 - Koninklijke Maatschappij voor ...

Natuurkundige voordrachten I Nieuwe reeks 89
Migraine: de ontrafeling van een complexe ziekte
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from the synaptic cleft. Therefore, loss-of-function
mutations in this protein will likely lead to increased
excitability. Support for this comes from a mutation
in SLC1A3 in a sporadic patient with migraine and
alternating hemiplegia. SLC1A3 codes for the EAAT1
glutamate transporter expressed in glial cells, and
functional studies of the mutant protein revealed dramatically
impaired glutamate transport. Moreover,
knocking down endogenous EAAT1 levels with antisense
oligonucleotides caused increased extracellular
glutamate levels and excitotoxicity.
C. FHM3
NaV1.1 is expressed primarily in inhibitory interneurons,
where a loss of function (e.g., as seen with
SMEI) would dampen inhibitory input, again leading
to overall increased excitability.
VIII. CONCLUDING REMARKS
Migraine is a multifactorial episodic disorder of
the brain, affecting a large percentage of the general
population. The high prevalence, combined
with the highly disabling nature of the disease,
causes migraine to rank as high impact on the lives
of patients and their families, as well as society as
a whole. Although many fundamental questions
remain unanswered, the work of many investigators
has greatly expanded our understanding of
the triggers and underlying mechanisms of the
migraine attack. The identification of FHM genes
has allowed the development of genetic screening
methods for diagnosing familial and sporadic hemiplegic
migraine. In addition, employing the power
of gene-targeting methods has yielded mouse models
of FHM, and these mice have proven valuable in
the study of the physiology of migraine, and will
undoubtedly help guide research in the development
of migraine prevention and treatment.
Het bovenstaande artikel verscheen in 2008 als hoofdstuk
3 in Advances in Genetics, Volume 63, Ion Channel
Diseases (Elsevier Inc.). Auteurs: C.F. Barrett, A.M.J.M. van
den Maagdenberg, R.R. Frants en M.D. Ferrari.
Via Rightslink verleende Elsevier toestemming tot
opneming van dit materiaal in het Jaarboek van Diligentia.