ArticleNeuropathology and applied neurobiology2019
Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes.
Article in Neuropathology and applied neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Associations of cognitive and behavioural impairment in ALS with brain pathology: pTDP-43 versus microglial activation.Journal of neurology · 2026Article
- C-terminal extension of HSPB6 in a family with myopathy and cataract.Human molecular genetics · 2026Article
- Regulation of physiological and pathological condensates by molecular chaperones.The FEBS journal · 2025Review
- Unlocking Disease-Modifying Treatments for TDP-43-Mediated Neurodegeneration.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Small Heat Shock Proteins: Protein Aggregation Amelioration and Neuro- and Age-Protective Roles.International journal of molecular sciences · 2025Review
- A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration.Nature communications · 2024Article
- Acetyl-L-carnitine and Amyotrophic Lateral Sclerosis: Current Evidence and Potential use.CNS & neurological disorders drug targets · 2024Review
- Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases.Nature communications · 2023Article
- Molecular Chaperones' Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis.Cells · 2023Review
- Machine learning hypothesis-generation for patient stratification and target discovery in rare disease: our experience with Open Science in ALS.Frontiers in computational neuroscience · 2023Article
- The Role of Small Heat Shock Proteins in Protein Misfolding Associated Motoneuron Diseases.International journal of molecular sciences · 2022Review
- The Multifaceted Neurotoxicity of Astrocytes in Ageing and Age-Related Neurodegenerative Diseases: A Translational Perspective.Frontiers in physiology · 2022Review
- Insights on Human Small Heat Shock Proteins and Their Alterations in Diseases.Frontiers in molecular biosciences · 2022Review
- Imaging immunological processes from blood to brain in amyotrophic lateral sclerosis.Clinical and experimental immunology · 2021Review
- Interplay between immunity and amyotrophic lateral sclerosis: Clinical impact.Neuroscience and biobehavioral reviews · 2021Review
- The Role of HSPB8, a Component of the Chaperone-Assisted Selective Autophagy Machinery, in Cancer.Cells · 2021Review
- [Rare variants of HSPB1 are probably associated with amyotrophic lateral sclerosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- Glial Cells-The Strategic Targets in Amyotrophic Lateral Sclerosis Treatment.Journal of clinical medicine · 2020Review
- PRDX2 protects against oxidative stress induced by H. pylori and promotes resistance to cisplatin in gastric cancer.Redox biology · 2020Article
- Metabolic Regulation of Glial Phenotypes: Implications in Neuron-Glia Interactions and Neurological Disorders.Frontiers in cellular neuroscience · 2020Review
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsAmyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by progressive loss of motor neurons, muscle weakness, spasticity, paralysis and death usually within 2-5 years of onset. Neuroinflammation is a hallmark of ALS pathology characterized by activation of glial cells, which respond by upregulating small heat shock proteins (HSPBs), but the exact underlying pathological mechanisms are still largely unknown. Here, we investigated the association between ALS disease duration, lower motor neuron loss, TARDNA-binding protein 43 (TDP-43) pathology, neuroinflammation and HSPB expression.
methodsWith immunohistochemistry, we examined HSPB1, HSPB5, HSPB6, HSPB8 and HSP16.2 expression in cervical, thoracic and sacral spinal cord regions in 12 ALS cases, seven with short disease duration (SDD), five with moderate disease duration (MDD), and ten age-matched controls. Expression was quantified using ImageJ to examine HSP expression, motor neuron numbers, microglial and astrocyte density and phosphorylated TDP-43 (pTDP-43+) inclusions.
resultsSDD was associated with elevated HSPB5 and 8 expression in lateral tract astrocytes, while HSP16.2 expression was increased in astrocytes in MDD cases. SDD cases had higher numbers of motor neurons and microglial activation than MDD cases, but similar levels of motor neurons with pTDP-43+ inclusions.
conclusionsIncreased expression of several HSPBs in lateral column astrocytes suggests that astrocytes play a role in the pathogenesis of ALS. SDD is associated with increased microgliosis, HSPB5 and 8 expression in astrocytes, and only minor changes in motor neuron loss. This suggests that the interaction between motor neurons, microglia and astrocytes determines neuronal fate and functional decline in ALS.
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