Biology Reference
In-Depth Information
Acute block
Threshold
rate for axon
survival
Age
Figure 5.3. Age-related decline in axonal transport and the threshold for disease. The decline in
axonal transport with age could predispose or even trigger neurodegenerative disease
below a certain threshold (dashed line). The reasons for falling below this threshold may
include acute events such as toxins, viruses, or demyelination that lead to a sudden
decline in transport (red line), cumulative events such as metabolic disorders causing
accelerated declines over a long period (green line), or a lower starting point,
for example, due to polymorphisms in transport regulating proteins (orange line).
(Fig. 5.3), just as amyloid pathology worsens when axonal transport is deliber-
ately impaired (Stokin
, 2005). Similarly, the decline in transport with age
could underlie the age-associated axonal swelling found in YFP-H transgenic
mice (Bridge
et al.
et al.
, 2007).
H. No parking! Could increased axonal transport be too much of
a “good” thing?
Finally, axonal disorders are so frequently associated with impaired transport that
it is tempting to assume that enhancing transport can only be good for axonal
health. However, when mitochondrial movement in axons is increased by
deleting the mitochondrial docking protein syntaphilin, this reduces the density
of mitochondria in axons and presynaptic terminals, thus impairing calcium
buffering at nerve terminals (Kang
et al.
, 2008). There are also subtle but
significant motor defects.
