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2017 ; 54
(4
): 2636-2658
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Insulin-Like Growth Factor-II/Cation-Independent Mannose 6-Phosphate Receptor in
Neurodegenerative Diseases
#MMPMID26993302
Wang Y
; MacDonald RG
; Thinakaran G
; Kar S
Mol Neurobiol
2017[May]; 54
(4
): 2636-2658
PMID26993302
show ga
The insulin-like growth factor II/mannose 6-phosphate (IGF-II/M6P) receptor is a
multifunctional single transmembrane glycoprotein. Recent studies have advanced
our understanding of the structure, ligand-binding properties, and trafficking of
the IGF-II/M6P receptor. This receptor has been implicated in a variety of
important cellular processes including growth and development, clearance of
IGF-II, proteolytic activation of enzymes, and growth factor precursors, in
addition to its well-known role in the delivery of lysosomal enzymes. The
IGF-II/M6P receptor, distributed widely in the central nervous system, has
additional roles in mediating neurotransmitter release and memory
enhancement/consolidation, possibly through activating IGF-II-related
intracellular signaling pathways. Recent studies suggest that overexpression of
the IGF-II/M6P receptor may have an important role in regulating the levels of
transcripts and proteins involved in the development of Alzheimer's disease
(AD)-the prevalent cause of dementia affecting the elderly population in our
society. It is reported that IGF-II/M6P receptor overexpression can increase the
levels/processing of amyloid precursor protein leading to the generation of
?-amyloid peptide, which is associated with degeneration of neurons and
subsequent development of AD pathology. Given the significance of the receptor in
mediating the transport and functioning of the lysosomal enzymes, it is being
considered for therapeutic delivery of enzymes to the lysosomes to treat
lysosomal storage disorders. Notwithstanding these results, additional studies
are required to validate and fully characterize the function of the IGF-II/M6P
receptor in the normal brain and its involvement in various neurodegenerative
disorders including AD. It is also critical to understand the interaction between
the IGF-II/M6P receptor and lysosomal enzymes in neurodegenerative processes,
which may shed some light on developing approaches to detect and prevent
neurodegeneration through the dysfunction of the receptor and the
endosomal-lysosomal system.