Neurological Impact of Type I Interferon Dysregulation DOI Creative Commons
Alessio Mylonas

IntechOpen eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: July 31, 2024

Type I interferons are a class of potent and tightly regulated cytokines important for antiviral anti-tumoural innate adaptive immunity. Dysregulated production can have serious neurologic consequences as exemplified in family rare diseases called type interferonopathies. Interferonopathies represent group genetically determined conditions characterised by upregulated interferon causing spectrum neuroinflammatory systemic manifestations. This chapter delves into the historical discovery interferons, their role immunity, subsequent identification interferonopathies placing emphasis on mechanisms dysfunction that often dominate clinical picture. The insights gained from studying these offer valuable lessons neurodegenerative neuropsychiatric which demonstrate considerable overlap with interferonopathies, underscoring broader significance more common diseases. Relevant therapeutic strategies targeting this pathway discussed, emphasising need brain-penetrant approaches.

Language: Английский

The neuroimmune nexus: unraveling the role of the mtDNA-cGAS-STING signal pathway in Alzheimer’s disease DOI Creative Commons

Shuiyue Quan,

Xiaofeng Fu,

Huimin Cai

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 4, 2025

The relationship between Alzheimer's disease (AD) and neuroimmunity has gradually begun to be unveiled. Emerging evidence indicates that cyclic GMP-AMP synthase (cGAS) acts as a cytosolic DNA sensor, recognizing damage-associated molecular patterns (DAMPs), inducing the innate immune response by activating stimulator of interferon genes (STING). Dysregulation this pathway culminates in AD-related neuroinflammation neurodegeneration. A substantial body mitochondria are involved critical pathogenic mechanisms AD, whose damage leads release mitochondrial (mtDNA) into extramitochondrial space. This leaked mtDNA serves DAMP, various pattern recognition receptors defense networks brain, including cGAS-STING pathway, ultimately leading an imbalance homeostasis. Therefore, modulation mtDNA-cGAS-STING restore neuroimmune homeostasis may offer promising prospects for improving AD treatment outcomes. In review, we focus on during stress activation pathway. Additionally, delve research progress further discuss primary directions potential hurdles developing targeted therapeutic drugs, gain deeper understanding pathogenesis provide new approaches its therapy.

Language: Английский

Citations

5
ApoE3 R136S binds to Tau and blocks its propagation, suppressing neurodegeneration in mice with Alzheimer’s disease DOI
Guiqin Chen, Mengmeng Wang, Zhentao Zhang

et al.

Neuron, Journal Year: 2025, Volume and Issue: 113(5), P. 719 - 736.e5

Published: Jan. 14, 2025

Language: Английский

Citations

2
Identification and development of cGAS inhibitors and their uses to treat Alzheimer's disease DOI Creative Commons
Jazmín Alarcón‐Espósito, Nagiri Ravi Kumar, Li Gan

et al.

Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00536 - e00536

Published: Jan. 1, 2025

Language: Английский

Citations

2
APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology DOI Creative Commons
Kristine M. Tran, Nellie Kwang, Claire A. Butler

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 22, 2025

Language: Английский

Citations

0
Distinct factors drive the progression of tau pathology in Alzheimer's disease DOI Creative Commons
Yifan Luo,

Honglu Yu,

Keqiang Ye

et al.

Fundamental Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology DOI Creative Commons
Kristine M. Tran, Nellie Kwang, Ángela Gómez-Arboledas

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 4, 2024

Apolipoprotein E ε4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD). A recent case report identified a rare variant in APOE, APOE3-R136S (Christchurch), proposed to confer resistance autosomal dominant Disease (AD). However, it remains unclear whether and how this exerts its protective effects.

Language: Английский

Citations

1
AAVrh.10 Delivery of Novel APOE2-Christchurch Variant Suppresses Amyloid and Tau Pathology in Alzheimer’s Disease Mice DOI
Caner Günaydın, Dolan Sondhi,

Stephen M. Kaminsky

et al.

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(12), P. 4303 - 4318

Published: Nov. 6, 2024

Language: Английский

Citations

1
Neurological Impact of Type I Interferon Dysregulation DOI Creative Commons
Alessio Mylonas

IntechOpen eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: July 31, 2024

Type I interferons are a class of potent and tightly regulated cytokines important for antiviral anti-tumoural innate adaptive immunity. Dysregulated production can have serious neurologic consequences as exemplified in family rare diseases called type interferonopathies. Interferonopathies represent group genetically determined conditions characterised by upregulated interferon causing spectrum neuroinflammatory systemic manifestations. This chapter delves into the historical discovery interferons, their role immunity, subsequent identification interferonopathies placing emphasis on mechanisms dysfunction that often dominate clinical picture. The insights gained from studying these offer valuable lessons neurodegenerative neuropsychiatric which demonstrate considerable overlap with interferonopathies, underscoring broader significance more common diseases. Relevant therapeutic strategies targeting this pathway discussed, emphasising need brain-penetrant approaches.

Language: Английский

Citations

0