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Alexander Disease (Alexander's Disease)

Rare leukoencephalopathy with infantile-onset accumulation of Rosenthal fibers in the subpial, periventricular, and subependymal zones of the brain. Rosenthal fibers are GLIAL FIBRILLARY ACIDIC PROTEIN aggregates found in ASTROCYTES. Juvenile- and adult-onset types show progressive atrophy of the lower brainstem instead. De novo mutations in the GFAP gene are associated with the disease with propensity for paternal inheritance.
Also Known As:
Alexander's Disease; Demyelinogenic Leukodystrophy; Dysmyelinogenic Leukodystrophy; Fibrinoid Degeneration of Astrocytes; Leukodystrophy with Rosenthal Fibers; Alexanders Disease
Networked: 244 relevant articles (5 outcomes, 12 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1. Neurodegenerative Diseases (Neurodegenerative Disease)
2. Multiple Sclerosis
3. Brain Ischemia (Cerebral Ischemia)
4. Nervous System Diseases (Neurological Disorders)
5. Alzheimer Disease (Alzheimer's Disease)

Experts

1. Messing, Albee: 33 articles (11/2021 - 03/2005)
2. Hagemann, Tracy L: 18 articles (01/2022 - 08/2005)
3. Goldman, James E: 17 articles (01/2022 - 03/2005)
4. Brenner, Michael: 13 articles (01/2020 - 10/2004)
5. Ceccherini, Isabella: 12 articles (12/2021 - 01/2008)
6. Yoshida, Tomokatsu: 12 articles (12/2021 - 07/2009)
7. Perng, Ming-Der: 11 articles (01/2022 - 10/2008)
8. Sechi, GianPietro: 9 articles (01/2021 - 03/2010)
9. Bachetti, Tiziana: 8 articles (01/2021 - 04/2008)
10. Nakagawa, Masanori: 8 articles (10/2019 - 03/2002)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Alexander Disease:
1. Glial Fibrillary Acidic ProteinIBA
2. Proteins (Proteins, Gene)FDA Link
3. Proteasome Endopeptidase Complex (Proteasome)IBA
12/15/2006 - "Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease."
04/02/2010 - "The accumulation of the intermediate filament protein, glial fibrillary acidic protein (GFAP), in astrocytes of Alexander disease (AxD) impairs proteasome function in astrocytes. "
04/02/2010 - "Oligomers of mutant glial fibrillary acidic protein (GFAP) Inhibit the proteasome system in alexander disease astrocytes, and the small heat shock protein alphaB-crystallin reverses the inhibition."
07/01/2008 - "The proteasome system is responsible for unfolded, short-lived proteins, which precludes the clearance of oligomeric and aggregated proteins, whereas macroautophagy, a process generally referred to as autophagy, mediates mainly the bulk degradation of long-lived cytoplasmic proteins, large protein complexes or organelles.1 Recently, the autophagy-lysosomal pathway has been implicated in neurodegenerative disorders as an important pathway for the clearance of abnormally accumulated intracellular proteins, such as huntingtin, tau, and mutant and modified α-synuclein.1-6 Our recent study illustrated the induction of adaptive autophagy in response to mutant glial fibrillary acidic protein (GFAP) accumulation in astrocytes, in the brains of patients with Alexander disease (AxD), and in mutant GFAP knock-in mouse brains.7 This autophagic response is negatively regulated by mammalian target of rapamycin (mTOR). "
07/01/2008 - "The proteasome system is responsible for unfolded, short-lived proteins, which precludes the clearance of oligomeric and aggregated proteins, whereas macroautophagy, a process generally referred to as autophagy, mediates mainly the bulk degradation of long-lived cytoplasmic proteins, large protein complexes or organelles.(1) Recently, the autophagy-lysosomal pathway has been implicated in neurodegenerative disorders as an important pathway for the clearance of abnormally accumulated intracellular proteins, such as huntingtin, tau and mutant and modified alpha-synuclein.(1-6) Our recent study illustrated the induction of adaptive autophagy in response to mutant glial fibrillary acidic protein (GFAP) accumulation in astrocytes, in the brains of patients with Alexander disease (AxD), and in mutant GFAP knock-in mouse brains.(7) This autophagic response is negatively regulated by mammalian target of rapamycin (mTOR). "
4. TOR Serine-Threonine KinasesIBA
07/01/2008 - "The proteasome system is responsible for unfolded, short-lived proteins, which precludes the clearance of oligomeric and aggregated proteins, whereas macroautophagy, a process generally referred to as autophagy, mediates mainly the bulk degradation of long-lived cytoplasmic proteins, large protein complexes or organelles.1 Recently, the autophagy-lysosomal pathway has been implicated in neurodegenerative disorders as an important pathway for the clearance of abnormally accumulated intracellular proteins, such as huntingtin, tau, and mutant and modified α-synuclein.1-6 Our recent study illustrated the induction of adaptive autophagy in response to mutant glial fibrillary acidic protein (GFAP) accumulation in astrocytes, in the brains of patients with Alexander disease (AxD), and in mutant GFAP knock-in mouse brains.7 This autophagic response is negatively regulated by mammalian target of rapamycin (mTOR). "
07/01/2008 - "The proteasome system is responsible for unfolded, short-lived proteins, which precludes the clearance of oligomeric and aggregated proteins, whereas macroautophagy, a process generally referred to as autophagy, mediates mainly the bulk degradation of long-lived cytoplasmic proteins, large protein complexes or organelles.(1) Recently, the autophagy-lysosomal pathway has been implicated in neurodegenerative disorders as an important pathway for the clearance of abnormally accumulated intracellular proteins, such as huntingtin, tau and mutant and modified alpha-synuclein.(1-6) Our recent study illustrated the induction of adaptive autophagy in response to mutant glial fibrillary acidic protein (GFAP) accumulation in astrocytes, in the brains of patients with Alexander disease (AxD), and in mutant GFAP knock-in mouse brains.(7) This autophagic response is negatively regulated by mammalian target of rapamycin (mTOR). "
5. Ceftriaxone (Ceftriaxon)FDA LinkGeneric
6. Phenytoin (Dilantin)FDA LinkGeneric
7. LactamsIBA
8. Anti-Bacterial Agents (Antibiotics)IBA
9. SynucleinsIBA
10. Oxidopamine (6 Hydroxydopamine)IBA

Therapies and Procedures

1. Bone Marrow Transplantation (Transplantation, Bone Marrow)
2. Therapeutics
11/17/2021 - "Antisense therapy in a rat model of Alexander disease reverses GFAP pathology, white matter deficits, and motor impairment."
01/01/2018 - "Reduced cerebrospinal fluid monoamines in Alexander's disease: a clue to a symptomatic therapy."
11/01/2006 - "TRH therapy in a patient with juvenile Alexander disease."
01/01/2021 - "Ketogenic Diet Therapy for Intractable Epilepsy in Infantile Alexander Disease: A Small Case Series and Analyses of Astroglial Chemokines and Proinflammatory Cytokines."
01/01/2020 - ": 4H: Hypomyelination, hypogonadotropic hypogonadism and hypodontia; AAV: Adeno-associated virus; AD: autosomal dominant; AGS: Aicardi-Goutieres syndrome; ALSP: Axonal spheroids and pigmented glia; APGBD: Adult polyglucosan body disease; AR: autosomal recessive; ASO: Antisense oligonucleotide therapy; AxD: Alexander disease; BAEP: Brainstem auditory evoked potentials; CAA: Cerebral amyloid angiopathy; CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASAL: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy; CARASIL: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; CGH: Comparative genomic hybridization; ClC2: Chloride Ion Channel 2; CMTX: Charcot-Marie-Tooth disease, X-linked; CMV: Cytomegalovirus; CNS: central nervous system; CRISP/Cas9: Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9; gRNA: Guide RNA; CTX: Cerebrotendinous xanthomatosis; DNA: Deoxyribonucleic acid; DSB: Double strand breaks; DTI: Diffusion tensor imaging; FLAIR: Fluid attenuated inversion recovery; GAN: Giant axonal neuropathy; H-ABC: Hypomyelination with atrophy of basal ganglia and cerebellum; HBSL: Hypomyelination with brainstem and spinal cord involvement and leg spasticity; HCC: Hypomyelination with congenital cataracts; HEMS: Hypomyelination of early myelinated structures; HMG CoA: Hydroxy methylglutaryl CoA; HSCT: Hematopoietic stem cell transplant; iPSC: Induced pluripotent stem cells; KSS: Kearns-Sayre syndrome; L-2-HGA: L-2-hydroxy glutaric aciduria; LBSL: Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate; LCC: Leukoencephalopathy with calcifications and cysts; LTBL: Leukoencephalopathy with thalamus and brainstem involvement and high lactate; MELAS: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke; MERRF: Myoclonic epilepsy with ragged red fibers; MLC: Megalencephalic leukoencephalopathy with subcortical cysts; MLD: metachromatic leukodystrophy; MRI: magnetic resonance imaging; NCL: Neuronal ceroid lipofuscinosis; NGS: Next generation sequencing; ODDD: Oculodentodigital dysplasia; PCWH: Peripheral demyelinating neuropathy-central-dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschprung disease; PMD: Pelizaeus-Merzbacher disease; PMDL: Pelizaeus-Merzbacher-like disease; RNA: Ribonucleic acid; TW: T-weighted; VWM: Vanishing white matter; WES: whole exome sequencing; WGS: whole genome sequencing; X-ALD: X-linked adrenoleukodystrophy; XLD: X-linked dominant; XLR: X-linked recessive."
3. Precision Medicine
4. Ketogenic Diet
5. Ventriculoperitoneal Shunt