Common mechanisms underlying axonal transport deficits in neurodegenerative diseases: a mini review

Yang, Xiaoman; Ma, Zhuoran; Lian, Piaopiao; Xu, Yan; Cao, Xin

doi:10.3389/fnmol.2023.1172197

Cited by 11 publications

(3 citation statements)

References 108 publications

(127 reference statements)

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“…Decreases in the expressions of genes for proteins, including tubulins, kinesins, and dyneins, which are involved in anterograde and retrograde axonal transport, were previously shown in DAergic neurons of the SN of patients with PD [52]. Impaired axonal transport is considered an important characteristic of this disease [80,81]. Our results show that axonal transport is also impaired in PD models, as manifested by decreased expressions of genes encoding microtubule structural proteins and proteins regulating microtubule stability in the SN.…”

Section: Diseasesupporting

confidence: 75%

Application of OpenArray Technology to Assess Changes in the Expression of Functionally Significant Genes in the Substantia Nigra of Mice in a Model of Parkinson’s Disease

Troshev,

Kolacheva,

Pavlova

et al. 2023

Genes

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Studying the molecular mechanisms of the pathogenesis of Parkinson’s disease (PD) is critical to improve PD treatment. We used OpenArray technology to assess gene expression in the substantia nigra (SN) cells of mice in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD and in controls. Among the 11 housekeeping genes tested, Rps27a was taken as the reference gene due to its most stable expression in normal and experimental conditions. From 101 genes encoding functionally significant proteins of nigrostriatal dopaminergic neurons, 57 highly expressed genes were selected to assess their expressions in the PD model and in the controls. The expressions of Th, Ddc, Maoa, Comt, Slc6a3, Slc18a2, Drd2, and Nr4a2 decreased in the experiment compared to the control, indicating decreases in the synthesis, degradation, and transport of dopamine and the impaired autoregulation of dopaminergic neurons. The expressions of Tubb3, Map2, Syn1, Syt1, Rab7, Sod1, Cib1, Gpx1, Psmd4, Ubb, Usp47, and Ctsb genes were also decreased in the MPTP-treated mice, indicating impairments of axonal and vesicular transport and abnormal functioning of the antioxidant and ubiquitin-proteasome systems in the SN. The detected decreases in the expressions of Snca, Nsf, Dnm1l, and Keap1 may serve to reduce pathological protein aggregation, increase dopamine release in the striatum, prevent mitophagy, and restore the redox status of SN cells.

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Section: Diseasesupporting

confidence: 75%

Application of OpenArray Technology to Assess Changes in the Expression of Functionally Significant Genes in the Substantia Nigra of Mice in a Model of Parkinson’s Disease

Troshev,

Kolacheva,

Pavlova

et al. 2023

Genes

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“…Another major factor that is yet to be explored is the migratory properties of different nanomaterials in the diseased brain (such as Alzheimer’s disease and Parkinson’s disease) as the CSF flow and axonal transport are altered compared to a healthy brain. , …”

Section: Resultsmentioning

confidence: 99%

Unilateral Administration of Surface-Modified G1 and G4 PAMAM Dendrimers in Healthy Mice to Assess Dendrimer Migration in the Brain

Srinageshwar,

Thompson,

Otero

et al. 2024

ACS Appl. Mater. Interfaces

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Polyamidoamine (PAMAM) dendrimers are nanoparticles that have a wide scope in the field of biomedicine. Previous evidence shows that the generation 4 (G4) dendrimers with a 100% amine surface (G4-NH 2 ) are highly toxic to cells in vitro and in vivo due to their positively charged amine groups. To reduce the toxicity, we modified the surface of the dendrimers to have more neutral functional groups, with 10% of the surface covered with −NH 2 and 90% of the surface covered with hydroxyl groups (−OH; G4−90/10). Our previous in vitro data show that these modified dendrimers are taken up by cells, neurons, and different types of stem cells in vitro and neurons and glial cells in vivo. The toxicity assay shows that these modified dendrimers are less toxic compared with G4-NH2 dendrimers. Moreover, prolonged dendrimer exposure (G1−90/10 and G4−90/10), up to 3 weeks following unilateral intrastriatal injections into the striatum of mice, showed that dendrimers have the tendency to migrate within the brain via corpus callosum at different rates depending on their size. We also found that there is a difference in migration between the G1 and G4 dendrimers based on their size differences. The G4 dendrimers migrate in the anterior and posterior directions as well as more laterally from the site of injection in the striatum compared to the G1 dendrimers. Moreover, the G4 dendrimers have unique projections from the site of injection to the cortical areas.

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“…244 Several pathological features and shared mechanisms related to axonal transport deficits in AD, PD, and other neuronal diseases are also narrated well. 245…”

Section: Ad and Pd: Common Featuresmentioning

confidence: 99%

Communal interaction of glycation and gut microbes in diabetes mellitus, Alzheimer's disease, and Parkinson's disease pathogenesis

Patil,

Tupe

2023

Medicinal Research Reviews

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Diabetes and its complications, Alzheimer's disease (AD), and Parkinson's disease (PD) are increasing gradually, reflecting a global threat vis‐à‐vis expressing the essentiality of a substantial paradigm shift in research and remedial actions. Protein glycation is influenced by several factors, like time, temperature, pH, metal ions, and the half‐life of the protein. Surprisingly, most proteins associated with metabolic and neurodegenerative disorders are generally long‐lived and hence susceptible to glycation. Remarkably, proteins linked with diabetes, AD, and PD share this characteristic. This modulates protein's structure, aggregation tendency, and toxicity, highlighting renovated attention. Gut microbes and microbial metabolites marked their importance in human health and diseases. Though many scientific shreds of evidence are proposed for possible change and dysbiosis in gut flora in these diseases, very little is known about the mechanisms. Screening and unfolding their functionality in metabolic and neurodegenerative disorders is essential in hunting the gut treasure. Therefore, it is imperative to evaluate the role of glycation as a common link in diabetes and neurodegenerative diseases, which helps to clarify if modulation of nonenzymatic glycation may act as a beneficial therapeutic strategy and gut microbes/metabolites may answer some of the crucial questions. This review briefly emphasizes the common functional attributes of glycation and gut microbes, the possible linkages, and discusses current treatment options and therapeutic challenges.

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Common mechanisms underlying axonal transport deficits in neurodegenerative diseases: a mini review

Cited by 11 publications

References 108 publications

Application of OpenArray Technology to Assess Changes in the Expression of Functionally Significant Genes in the Substantia Nigra of Mice in a Model of Parkinson’s Disease

Application of OpenArray Technology to Assess Changes in the Expression of Functionally Significant Genes in the Substantia Nigra of Mice in a Model of Parkinson’s Disease

Unilateral Administration of Surface-Modified G1 and G4 PAMAM Dendrimers in Healthy Mice to Assess Dendrimer Migration in the Brain

Communal interaction of glycation and gut microbes in diabetes mellitus, Alzheimer's disease, and Parkinson's disease pathogenesis

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