Essential tremor (ET) is one of the most prevalent neurological disorders
worldwide. ET presents mainly with kinetic and action tremor in upper limbs. Tremor
may also affect the head and some patients develop an ataxic gait, as well as
cognitive/affective symptoms. ET significantly impacts the quality of life. There is
accumulating evidence that ET is a slowly progressive neurodegenerative disease,
driven by both genetic and environmental (possibly dietary) factors. Both the olivocerebellar
pathways and the cerebellar cortex are critically involved, with particular
impairments in the morphology of the Purkinje neurons (Purkinjopathy) as well as the
surrounding micro-circuitry. Dysfunctional cerebello-thalamo-cortical loops probably
result in bursts of tremor. So far, only few symptomatic medications are available,
including beta-blockers, primidone and drugs aiming to modulate GABAergic
transmission such as topiramate or gabapentine. Surgery (deep brain stimulation,
thalamotomy) is proposed to refractory cases but carries the risk of infection, bleeding
in the brain and several technical issues related to the mispositioning of electrodes.
MRI-guided focused ultrasound is a promising technique, but long-term follow-up is
missing. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct
current stimulation (tDCS) are encouraging non-invasive techniques but no consensus
on optimal protocols has been reached so far. It is remarkable to observe that none of
the available therapies targets the neurodegenerative process affecting in particular the
cerebellum, the masterpiece of progression of the disease. This chapter focuses on the
pathogenesis of ET and discusses possible novel avenues for therapy and prevention. In
particular, the impact of environmental toxins such as beta-carboline alkaloids (βCAs),
possibly generated from Maillard-type reaction products, is discussed. Animal models
of ET, toxicokinetics and neurotoxic effects of βCAs are presented, with an emphasis
on the neuroprotective pathways that are candidates to block the neurodegenerative
process. Moreover, we consider a group of enzymes that could be neuroprotective,
especially GAD65 and GAD67, involved in GABA synthesis/neurotransmission, and
MAOA/MAOB. Finally, we emphasize the potential interest of dietary phytochemicals (such as phenolic acids, catechins, flavonoids, anthocyans, stilbenoids, curcuminoids)
and herbal therapies (based i.e. on Bacopa monnieri, Ginkgo biloba) as neuroprotective
approaches to hamper the neurodegenerative process in ET.
Keywords: β-Carboline Alkaloids, Chemoprevention, CNS Disorder, Deep Brain
Stimulation of the Thalamus, Essential Tremor (ET), ET Pharmacotherapy, ET
Animal Model, (GABA)ergic Dysfunction, Gamma Knife Surgery (GK),
Harmane, Harmaline, Maillard Reaction, Neuroprotection, Neurodegenerative,
Neurotoxicity, Purkinje Neurons, Repetitive Transcranial Magnetic Stimulation
(rTMS), Thalamotomy.
