Abstract:
:Neuroinflammation and neurodegeneration are key components in the establishment and progression of neurodegenerative diseases including Alzheimer's Disease (AD). Over the past decade increasing evidence is emerging for the use of components of the canonical autophagy machinery in pathways that are characterized by LC3 lipidation yet are distinct from traditional macro-autophagy. One such pathway that utilizes components of the autophagy machinery to target LC3 to endosomes, a process termed LC3-associated endocytosis (LANDO), has recently been identified and regulates neuroinflammation. Abrogation of LANDO in microglia cells results in a propensity for elevated neuroinflammatory cytokine production. Using the well-established 5xFAD model of AD to interrogate neuroinflammatory regulation, impairment of LANDO through deletion of a key upstream regulator Rubicon or other downstream autophagy components, exacerbated disease onset and severity, while deletion of microglial autophagy alone had no measurable effect. Mice presented with robust deposition of the neurotoxic AD protein β-amyloid (Aβ), microglial activation and inflammatory cytokine production, tau phosphorylation, and aggressive neurodegeneration culminating in severe memory impairment. LANDO-deficiency impaired recycling of receptors that recognize Aβ, including TLR4 and TREM2. LANDO-deficiency alone through deletion of the WD-domain of the autophagy protein ATG16L, revealed a role for LANDO in the spontaneous establishment of age-associated AD. LANDO-deficient mice aged to 2 years presented with advanced AD-like disease and pathology correlative to that observed in human AD patients. Together, these studies illustrate an important role for microglial LANDO in regulating CNS immune activation and protection against neurodegeneration. New evidence is emerging that demonstrates a putative linkage between pathways such as LANDO and cell death regulation via apoptosis and possibly necroptosis. Herein, we provide a review of the use of the autophagy machinery in non-canonical mechanisms that alter immune regulation and could have significant impact in furthering our understanding of not only CNS diseases like AD, but likely beyond.
journal_name
Neural Regen Resjournal_title
Neural regeneration researchauthors
Rickman AD,Hilyard A,Heckmann BLdoi
10.4103/1673-5374.317958keywords:
["Alzheimer’s disease","LC3-associated endocytosis","aging","autophagy","inflammation","microglia","neurodegeneration","neuroinflammation"]subject
Has Abstractpub_date
2022-02-01 00:00:00pages
246-250issue
2eissn
1673-5374issn
1876-7958pii
NeuralRegenRes_2022_17_2_246_317958journal_volume
17pub_type
杂志文章,评审abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.01.008
更新日期:2013-01-05 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.10.006
更新日期:2013-04-05 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.11.005
更新日期:2013-04-15 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.12.004
更新日期:2013-04-25 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.13.004
更新日期:2013-05-05 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.14.005
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abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.15.005
更新日期:2013-05-25 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.16.004
更新日期:2013-06-05 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.17.005
更新日期:2013-06-15 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.18.004
更新日期:2013-06-25 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.19.004
更新日期:2013-07-05 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.02.005
更新日期:2013-01-15 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.20.003
更新日期:2013-07-15 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.21.003
更新日期:2013-07-25 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.22.004
更新日期:2013-08-05 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.23.004
更新日期:2013-08-15 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.24.003
更新日期:2013-08-25 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.25.004
更新日期:2013-09-05 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.26.004
更新日期:2013-09-15 00:00:00
abstract::An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This in...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.27.004
更新日期:2013-09-25 00:00:00
abstract::We report the complete mitochondrial genome of the fish Salminus brasiliensis, popularly known as dourado. It is a circular, 17,721 bp long DNA molecule, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding Control Region of 2128 bp, a relatively large molecule when compared to other closel...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.28.004
更新日期:2013-10-05 00:00:00
abstract::We report the complete mitochondrial genome of the fish Salminus brasiliensis, popularly known as dourado. It is a circular, 17,721 bp long DNA molecule, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding Control Region of 2128 bp, a relatively large molecule when compared to other closel...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.29.004
更新日期:2013-10-15 00:00:00
abstract::We report the complete mitochondrial genome of the fish Salminus brasiliensis, popularly known as dourado. It is a circular, 17,721 bp long DNA molecule, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding Control Region of 2128 bp, a relatively large molecule when compared to other closel...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.03.005
更新日期:2013-01-25 00:00:00
abstract::We report the complete mitochondrial genome of the fish Salminus brasiliensis, popularly known as dourado. It is a circular, 17,721 bp long DNA molecule, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding Control Region of 2128 bp, a relatively large molecule when compared to other closel...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.30.004
更新日期:2013-10-25 00:00:00
abstract::We report the complete mitochondrial genome of the fish Salminus brasiliensis, popularly known as dourado. It is a circular, 17,721 bp long DNA molecule, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding Control Region of 2128 bp, a relatively large molecule when compared to other closel...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.31.005
更新日期:2013-11-05 00:00:00
abstract::We report the complete mitochondrial genome of the fish Salminus brasiliensis, popularly known as dourado. It is a circular, 17,721 bp long DNA molecule, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding Control Region of 2128 bp, a relatively large molecule when compared to other closel...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.32.006
更新日期:2013-11-15 00:00:00
abstract::We report the complete mitochondrial genome of the fish Salminus brasiliensis, popularly known as dourado. It is a circular, 17,721 bp long DNA molecule, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding Control Region of 2128 bp, a relatively large molecule when compared to other closel...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.33.006
更新日期:2013-11-25 00:00:00
abstract::We report the complete mitochondrial genome of the fish Salminus brasiliensis, popularly known as dourado. It is a circular, 17,721 bp long DNA molecule, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding Control Region of 2128 bp, a relatively large molecule when compared to other closel...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.34.006
更新日期:2013-12-05 00:00:00
abstract::We report the complete mitochondrial genome of the fish Salminus brasiliensis, popularly known as dourado. It is a circular, 17,721 bp long DNA molecule, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding Control Region of 2128 bp, a relatively large molecule when compared to other closel...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.35.006
更新日期:2013-12-15 00:00:00
abstract::We report the complete mitochondrial genome of the fish Salminus brasiliensis, popularly known as dourado. It is a circular, 17,721 bp long DNA molecule, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a non-coding Control Region of 2128 bp, a relatively large molecule when compared to other closel...
journal_title:Neural regeneration research
pub_type: 杂志文章
doi:10.3969/j.issn.1673-5374.2013.36.006
更新日期:2013-12-25 00:00:00