Autophagy in Spinal Cord Motor Neurons in Sporadic Amyotrophic Lateral Sclerosis
Abstract
To assess the potential role of autophagy in amyotrophic lateral sclerosis (ALS), lumbar spinal cords in a total of 19 sporadic ALS cases and 27 age-matched controls were investigated. Immunohistochemical analysis using antibodies to the markers of autophagy microtubule-associated protein light chain 3 (LC3) and p62 was performed on samples from 12 ALS and 15 controls. Electron microscopy was performed on samples from 16 ALS and 15 controls, including overlapping cases. In the ALS cases, the somata of normal-appearing and degenerated motor neurons and round bodies were occasionally immunostained for LC3; round bodies and skein-like inclusions were immunostained for p62. By electron microscopy, all 16 ALS patients showed features of autophagy in the cytoplasm of normal-appearing motor neurons and, more frequently, in degenerated motor neurons. Autophagosomes surrounded by a double-membrane and autolysosomes isolated by a single membrane contained sequestered cytoplasmic organelles, such as mitochondria and ribosome-like structures. These autophagy features were also found in close association with the characteristic inclusions of ALS(i.e. round bodies, skein-like inclusions, and Bunina bodies); honeycomb-like structures also occasionally showed autophagy-associated features. Normal-appearing anterior horn neurons in control patients showed no autophagy features. Thus, autophagy seems to be activated and upregulated in the cytoplasm of motor neurons and may be involved in the mechanisms of neurodegeneration of motor neurons in sporadic ALS.
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Many studies in cellular and animal models of ALS indicate enhanced autophagy activity in ALS.
“Many studies in cellular and animal models of ALS indicate enhanced autophagy activity in ALS (Morimoto et al., 2007; Sasaki, 2011), in addition to the occurrence of autophagy-mediated clearance of mutant SOD1 and TDP-43 (Nassif et al., 2010).”
From Downregulation of MicroRNA-193b-3p Promotes Autophagy and Cell Survival by Targeting TSC1/mTOR Signaling in NSC-34 Cells (2017) · cites this paper as Sasaki, 2011
Failed or stalled clearance via autophagy occurs in sALS.
“suggesting failed or stalled clearance via autophagy.”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [273]
In humans with sALS, pathologic inclusions found in motor neurons are surrounded by LC3 and SQSTM1.
“In humans with sALS, pathologic inclusions found in motor neurons are surrounded by LC3 and SQSTM1 [273]”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [273]
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- Authors
- Sasaki, S.
- Affiliations
- Tokyo Women's Medical University (JP)
- Corresponding author
- Sasaki, Shoichi
- ORCID
- Sasaki, Shoichi
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-05
- Volume
- 70
- Issue
- 5
- Pages
- 349-359
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2317545246
- Cited by
- 249
- References
- 59
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 11 · 2023: 12 · 2022: 15 · 2021: 23 · 2020: 19 · 2019: 11 · 2018: 17 · 2017: 25 · 2016: 18 · 2015: 28 · 2014: 13 · 2013: 21 · 2012: 10
- FWCI
- 9.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- autophagy, sporadic ALS, motor neurons, spinal cord, LC3, p62, autophagosomes, autolysosomes, round bodies, Bunina bodies, honeycomb structure, neurodegeneration
- MeSH terms
- Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Autophagy, Inclusion Bodies, Female, Humans, Immunohistochemistry, Lumbar Vertebrae, Male, Microscopy, Electron, Middle Aged, Motor Neurons, Nerve Degeneration, Spinal Cord, Lewy Bodies
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