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Exp Neurobiol. 2013 Sep;22(3):133-42.
Neuronal autophagy and
neurodevelopmental disorders.
Lee KM1, Hwang SK, Lee JA.
Abstract
Neurodevelopmental disorders include a wide
range of diseases such as autism spectrum
disorders and mental retardation. Mutations in
several genes that regulate neural development
and synapse function have been identified in
neurodevelopmental disorders. Interestingly, some affected genes and pathways in
these diseases are associated with the autophagy
pathway. Autophagy is a complex, bulky
degradative process that involves the
sequestration of cellular proteins, RNA, lipids,
and cellular organelles into lysosomes.
Despite recent progress in elucidating the
genetics and molecular pathogenesis of these
disorders,
little is known
about the pathogenic mechanisms and autophagy-related
pathways involved in common neurodevelopmental
disorders.
Therefore, in this review, we focus on the
current understanding of neuronal autophagy as
well as recent findings on genetics and the
roles of autophagy pathway in common
neurodevelopmental disorders.
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Neurobiol Aging. 2014 May;35(5):941-57.
Autophagy in aging and
neurodegenerative diseases: implications for
pathogenesis and therapy.
Tan CC1, Yu JT2, Tan MS3, Jiang T4, Zhu XC4, Tan
L5.
Abstract
Neurodegenerative diseases, such as Alzheimer's
disease Parkinson's disease, Huntington's
disease, and amyotrophic lateral sclerosis, share a common cellular and molecular
pathogenetic mechanism involving aberrant
misfolded protein or peptide aggregation and
deposition.
Autophagy
represents a major route for degradation of
aggregated cellular proteins and dysfunctional
organelles.
Emerging studies have demonstrated that
up-regulation of
autophagy can lead to decreased levels of these
toxic aggregate-prone proteins,
and is beneficial in the context of aging and
various models of neurodegenerative diseases.
Understanding the signaling pathways
involved in the regulation of autophagy is
crucial to the development of strategies for
therapy. This review will discuss the
cellular and molecular mechanisms of autophagy
and its important role in the pathogenesis of
aging and neurodegenerative diseases, and the
ongoing drug discovery strategies for
therapeutic modulation.
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J Cell Sci. 2015 Apr 1;128(7):1259-67.
Autophagosome dynamics in
neurodegeneration at a glance.
Wong YC1, Holzbaur EL2.
Abstract
Autophagy is an essential homeostatic
process for degrading cellular cargo.
Aging organelles and protein aggregates are
degraded by the autophagosome-lysosome pathway,
which is
particularly crucial in neurons.
There is
increasing
evidence implicating defective autophagy in
neurodegenerative diseases,
including amyotrophic lateral sclerosis (ALS),
Alzheimer's disease, Parkinson's disease and
Huntington's disease. Recent work using
live-cell imaging has identified autophagy as a
predominantly polarized process in neuronal
axons; autophagosomes preferentially form at the
axon tip and undergo retrograde transport back
towards the cell body.
Autophagosomes engulf cargo including
damaged mitochondria (mitophagy) and protein
aggregates,
and subsequently fuse with lysosomes during
axonal transport to effectively degrade their
internalized cargo. In this Cell Science at a
Glance article and the accompanying poster,
we review recent progress on the
dynamics of the autophagy pathway in neurons
and highlight the defects observed at
each step of this pathway during
neurodegeneration.
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Int J Mol Sci. 2015 Nov 9;16(11):26797-812.
The Function of Autophagy
in Neurodegenerative Diseases.
Kiriyama Y1, Nochi H2.
Abstract
Macroautophagy, hereafter referred to as
autophagy, is a bulk degradation process
performed by lysosomes in which aggregated and
altered proteins as well as dysfunctional
organelles are decomposed. Autophagy is
a basic cellular process that maintains
homeostasis and is
crucial for
postmitotic neurons.
Thus,
impaired autophagic processes in neurons lead to
improper homeostasis and neurodegeneration.
Recent studies have suggested that
impairments of the autophagic process are
associated with several neurodegenerative
diseases, such as Alzheimer's disease,
Parkinson's disease, Huntington's disease,
amyotrophic lateral sclerosis, and static
encephalopathy of childhood with
neurodegeneration in adulthood. In this review,
we focus on the recent findings
regarding the autophagic process and the
involvement of autophagy in neurodegenerative
diseases.
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