Biology Reference
In-Depth Information
9.3
Conclusion
Functional amyloid in mammals is of particular interest because
amyloid deposition is a feature of many poorly understood and
presently untreatable human diseases (see Chapter 1). Before more
effective therapeutic approaches to amyloid disease can be designed
and implemented, a thorough understanding of the mechanisms
of amyloid toxicity is necessary. Clues about amyloid toxicity may
be gleaned from studying how organisms, particularly higher
organisms, regulate and control amyloid formation and degradation.
Furthermore, these regulatory mechanisms might be co-opted to
treat amyloid diseases.
One interesting question that remains unanswered is how
mammalian amyloid is degraded. Fibrin fibres are degraded by the
plasmin protease but these fibres likely contain only short amyloid-
like structures. Pmel17 forms fibres composed of cross-
-sheets
inside melanosomes. The fate of melanosomes in various tissues
is the subject of debate; in the skin, melanosomes are passed to
keratinocytes. Keratinocytes form the surface of the skin, so in the
skin, melanosomes are ultimately shed rather than being degraded.
Melanosomes in the eye cannot be shed, and their fate is not well
understood. Recent studies have suggested that higher organisms
might contain biological pathways for promoting amyloid formation
as well as degrading amyloid under pathological conditions.
β
It
is possible that such generalized systems exist for regulating the
formation and removal of functional amyloid.
In mammals, amyloid-like structures appear to fulfil two very
different functional roles — modulating the chemistry of melanin
synthesis and helping to regulate haemostasis. The fact that the two
known examples of mammalian functional amyloid are so divergent
demonstrates the potential range of functions amyloid can fulfil
(Fig. 9.5). It also suggests that many more instances of functional
amyloid may be found. The discovery of these two examples will
hopefully stimulate further efforts to identify and characterize
functional amyloid in mammals. Given the diversity and complexity
of mammalian cellular physiology, amyloid-like structures may be
found with novel and unexpected functions.
17
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