Therapeutic potential of ApoE-mimetic peptides in CNS disorders: Current perspective

Ahmed, Sakeel; Pande, Abhay H.; Sharma, Shyam Sunder

doi:10.1016/j.expneurol.2022.114051

Cited by 11 publications

(5 citation statements)

References 172 publications

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“…APOE can bind to a battery of receptors to mediate downstream biological effects, among which LRP1 is the most relevant receptor of APOE in the CNS with high affinity ( 41 , 42 ), which has been reported to be associated with the pathology of Alzheimer’s disease. In mice subjected to NMOSD model, we showed that LRP1 expression is down-regulated.…”

Section: Discussionmentioning

confidence: 99%

APOE from patient-derived astrocytic extracellular vesicles alleviates neuromyelitis optica spectrum disorder in a mouse model

Jiang,

Li,

et al. 2024

Sci. Transl. Med.

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Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy of the central nervous system, mediated by antibodies against aquaporin-4 water channel protein (AQP4-Abs), resulting in damage of astrocytes with subsequent demyelination and axonal damage. Extracellular communication through astrocyte-derived extracellular vesicles (ADEVs) has received growing interest in association with astrocytopathies. However, to what extent ADEVs contribute to NMOSD pathogenesis remains unclear. Here, through proteomic screening of patient-derived ADEVs, we observed an increase in apolipoprotein E (APOE)–rich ADEVs in patients with AQP4-Abs–positive NMOSD. Intracerebral injection of the APOE-mimetic peptide APOE 130–149 attenuated microglial reactivity, neuroinflammation, and brain lesions in a mouse model of NMOSD. The protective effect of APOE in NMOSD pathogenesis was further established by the exacerbated lesion volume in APOE-deficient mice, which could be rescued by exogenous APOE administration. Genetic knockdown of the APOE receptor lipoprotein receptor–related protein 1 (LRP1) could block the restorative effects of APOE 130–149 administration. The transfusion ADEVs derived from patients with NMOSD and healthy controls also alleviated astrocyte loss, reactive microgliosis, and demyelination in NMOSD mice. The slightly larger beneficial effect of patient-derived ADEVs as compared to ADEVs from healthy controls was further augmented in APOE −/− mice. These results indicate that APOE from astrocyte-derived extracellular vesicles could mediate disease-modifying astrocyte-microglia cross-talk in NMOSD.

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Section: Discussionmentioning

confidence: 99%

APOE from patient-derived astrocytic extracellular vesicles alleviates neuromyelitis optica spectrum disorder in a mouse model

Jiang,

Li,

et al. 2024

Sci. Transl. Med.

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“…However, we cannot conclusively rule out other potential ApoE2-mediated correction mechanisms such as increased uptake into affected cells via cross-correction, which is in line with our findings in MPS II fibroblasts and bEND.3 cells and with previous studies documenting an augmented uptake into neurons and glia of lysosomal proteins after ApoE2 tagging. 23 , 60 , 61 , 62 …”

Section: Discussionmentioning

confidence: 99%

Tagged IDS causes efficient and engraftment-independent prevention of brain pathology during lentiviral gene therapy for Mucopolysaccharidosis type II

Catalano,

Vlaar,

Katsavelis

et al. 2023

Molecular Therapy - Methods & Clinical Development

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“…In the CNS, APOE is produced predominantly by astrocytes and to some extent microglia. In addition, neurons express APOE in response to excitotoxic injury [68][69][70][71]. Given that these proteins play key roles in processes that appear to be dysfunctional in SMA, including synapse formation, axonal elongation, neuronal survival and plasticity, inflammation, and modulation of oxidative stress, the induction of these proteins by nusinersen could represent a parallel and synergistic positive effect associated with the increase in SMN protein.…”

Section: Apolipoproteinsmentioning

confidence: 99%

Identification of Novel Biomarkers of Spinal Muscular Atrophy and Therapeutic Response by Proteomic and Metabolomic Profiling of Human Biological Fluid Samples

et al. 2023

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Spinal muscular atrophy (SMA) is a neuromuscular disease resulting from mutations or deletions in SMN1 that lead to progressive death of alpha motor neurons, ultimately leading to severe muscle weakness and atrophy, as well as premature death in the absence of treatment. Recent approval of SMN-increasing medications as SMA therapy has altered the natural course of the disease. Thus, accurate biomarkers are needed to predict SMA severity, prognosis, drug response, and overall treatment efficacy. This article reviews novel non-targeted omics strategies that could become useful clinical tools for patients with SMA. Proteomics and metabolomics can provide insights into molecular events underlying disease progression and treatment response. High-throughput omics data have shown that untreated SMA patients have different profiles than controls. In addition, patients who clinically improved after treatment have a different profile than those who did not. These results provide a glimpse on potential markers that could assist in identifying therapy responders, in tracing the course of the disease, and in predicting its outcome. These studies have been restricted by the limited number of patients, but the approaches are feasible and can unravel severity-specific neuro-proteomic and metabolic SMA signatures.

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Therapeutic potential of ApoE-mimetic peptides in CNS disorders: Current perspective

Cited by 11 publications

References 172 publications

APOE from patient-derived astrocytic extracellular vesicles alleviates neuromyelitis optica spectrum disorder in a mouse model

APOE from patient-derived astrocytic extracellular vesicles alleviates neuromyelitis optica spectrum disorder in a mouse model

Tagged IDS causes efficient and engraftment-independent prevention of brain pathology during lentiviral gene therapy for Mucopolysaccharidosis type II

Identification of Novel Biomarkers of Spinal Muscular Atrophy and Therapeutic Response by Proteomic and Metabolomic Profiling of Human Biological Fluid Samples

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