3. Umbruch 4.4..2005 - Online Pot

Cannabinoids in neurodegeneration and neuroprotection 97
Recent data on the putative neuroprotective and anti-inflammatory properties
of cannabinoids have opened new perspectives that could be of interest in
AD. For instance, the contribution of CB 1 receptors in an in vitro model of AD
has been also studied by Milton [176]. This study shows that AEA and
noladin-ether are able to prevent Aβ-induced neurotoxicity through a CB 1
receptor-mediated mechanism. Thus, after exposure to different fibrilogenic
peptides, the two endocannabinoids, at nanomolar concentrations, were shown
to prevent their toxic effect on a neuronal cell line [176]. Furthermore, this protective
effect was reversed by the CB 1 receptor specific antagonist AM251, and
seemed to be mediated by the mitogen activated protein kinase pathway, since
a selective inhibitor for this signaling pathway also prevented the protective
effects of the two endocannabinoids [176]. Similar results have been recently
published by Iuvone et al. [177] using cultured PC12 cells. These authors
found a marked reduction in cell survival following exposure of cells to Aβ,
that was associated with increased reactive oxygen species production and
lipid peroxidation, as well as caspase 3 activation, DNA fragmentation and
increased intracellular calcium [177]. Interestingly, the treatment of the cells
with CBD prior to Aβ exposure significantly elevated cell survival while it
decreased oxidative stress, lipid peroxidation, caspase 3 levels, DNA fragmentation
and intracellular calcium [177]. The authors concluded that CBD
exerts a combination of neuroprotective, antioxidative and anti-apoptotic
effects against Aβ toxicity, and that inhibition of caspase 3 appearance from its
inactive precursor, pro-caspase 3, by CBD might be involved in the signalling
pathway for this neuroprotection [177].
Therefore, taken together, the data obtained in the above studies suggest that
cannabinoids could have an important role in the prevention of Aβ-induced
neurotoxicity and counteract some of its devastating effects. Without excluding
a role for CB 1 receptors or for other mechanisms available to certain
cannabinoids, these data suggest that part of these beneficial effects of
cannabinoids might be mediated by CB 2 receptors located on glial cells activated
by the inflammatory process elicited by maturation of senile plaques.
These effects would be similar to those described above concerning the
anti-inflammatory role of cannabinoids exerted through the modulation of several
cytotoxic mediators such as NO, TNF-α, cytokines and others (see [24,
68] for recent reviews).
MS
MS is the neurological disease that represents the most frequent cause of
non-traumatic, chronic disability in young adults (for review, see [178]). It is
an autoimmune disease that causes demyelination and axonal loss, in particular
in the spinal cord, resulting in a variety of neurological signs, among which
pain and motor impairment are the most characteristic [119]. It was initially
thought that neurological signs in MS were exclusively caused by inflamma-