Biomedical Engineering Reference
In-Depth Information
It has been suggested that aberrant processing of
b
PP and a conformational
transition from
a
-helix to
b
-sheet in the amino-terminal region of the amylo-
id
b
-peptide is linked to the formation of amyloid plaques [155, 156].
4.4
Lysosomal Storage Diseases
Several lysosomal storage diseases result from defective expression of specific
glycosidases. The intracellular accumulation of unprocessed carbohydrate sub-
strates leads to aberrant cellular structure and cell death. Thus, deficient
or defective hexosaminidase results in either Tay-Sachs or Sandhoff disease
[157]. Fucosidosis, another neurovisceral storage disease, is caused by defec-
tive
-
L
-fucosidase expression.
Aspartylglycosaminuria (AGU) is the most common disorder of glycoprotein
degradation and is caused by a deficiency of lysosomal glycosylasparaginase,
which hydrolyzes
a
-
N
-glycosidic bond between Asn and Gn, resulting in the
accumulation of asparatylglucosamine. The most prominent clinical findings
include severe mental and motor retardation. Most cases of AGU are caused by
a mutation in the gene that results in a failure to activate the enzyme precursor
by intramolecular autoproteolysis [158].
b
4.5
Other Diseases
A genetic defect of
a
-M II causes congenital dyserythropoietic anemia type II.
The reduction of
-M II activity results in a failure of polylactosaminoglycan
formation in erythrocyte membrane proteins, leading to clustering of mem-
brane proteins and formation of unstable erythrocytes [159].
Acute phase proteins are plasma proteins produced mainly by hepatocytes.
Most APPs are glycoproteins with one or more
N
-linked complex glycans.
Stimulants that commonly induce the acute phase response include tissue
injury, rheumatoid arthritis, bacterial infection, inflammation, and neo-
plasms. Cytokines, notably interleukin-6, induce striking alterations in the
concentration and glycosylation pattern of APPs in response to these stimuli
[160].
a
5
Choice of Expression Systems
5.1
Systems Available for Glycoprotein Expression
A number of recombinant proteins including peptide hormones, cytokines,
growth factors and monoclonal antibodies have been obtained using different
expression vectors and host cell systems [161]. However, it has been observed
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