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1.
Int J Mol Sci ; 22(22)2021 Nov 19.
Article in English | MEDLINE | ID: mdl-34830381

ABSTRACT

Huntington's disease (HD) is a rare neurodegenerative disorder caused by an expansion of CAG trinucleotide repeat located in the exon 1 of Huntingtin (HTT) gene in human chromosome 4. The HTT protein is ubiquitously expressed in the brain. Specifically, mutant HTT (mHTT) protein-mediated toxicity leads to a dramatic degeneration of the striatum among many regions of the brain. HD symptoms exhibit a major involuntary movement followed by cognitive and psychiatric dysfunctions. In this review, we address the conventional role of wild type HTT (wtHTT) and how mHTT protein disrupts the function of medium spiny neurons (MSNs). We also discuss how mHTT modulates epigenetic modifications and transcriptional pathways in MSNs. In addition, we define how non-cell autonomous pathways lead to damage and death of MSNs under HD pathological conditions. Lastly, we overview therapeutic approaches for HD. Together, understanding of precise neuropathological mechanisms of HD may improve therapeutic approaches to treat the onset and progression of HD.


Subject(s)
Epigenesis, Genetic , Huntingtin Protein/genetics , Huntington Disease/genetics , Neurons/metabolism , Animals , Brain/metabolism , Brain/pathology , Corpus Striatum/metabolism , Corpus Striatum/pathology , Disease Models, Animal , Humans , Huntington Disease/pathology , Neostriatum/metabolism , Neostriatum/pathology , Nerve Tissue Proteins/genetics , Neurons/pathology
2.
Appl Environ Microbiol ; 75(10): 3289-95, 2009 May.
Article in English | MEDLINE | ID: mdl-19304830

ABSTRACT

Fusarium graminearum is an important fungal pathogen of cereal crops and produces mycotoxins, such as the trichothecenes nivalenol and deoxynivalenol. This species may be subdivided into a series of genetic lineages or phylogenetic species. We identified strains of F. graminearum from the Republic of Korea to lineage, tested their ability to produce nivalenol and deoxynivalenol, and determined the genetic composition and structure of the populations from which they were recovered. Based on amplified fragment length polymorphism (AFLP), PCR genotyping, and chemical analyses of trichothecenes, all 249 isolates from southern provinces belonged to lineage 6, with 241 having the nivalenol genotype and 8 having the deoxynivalenol genotype. In the eastern Korea province, we recovered 84 lineage 6 isolates with the nivalenol genotype and 23 lineage 7 isolates with the deoxynivalenol genotype. Among 333 lineage 6 isolates, 36% of the AFLP bands were polymorphic, and there were 270 multilocus haplotypes. Genetic identity among populations was high (>0.972), and genotype diversity was low (30 to 58%). To test the adaptation of lineage 6 to rice, conidial mixtures of strains from lineages 3, 6, and 7 were inoculated onto rice plants and then recovered from the rice grains produced. Strains representing lineages 6 and 7 were recovered from inoculated spikelets at similar frequencies that were much higher than those for the strain representing lineage 3. Abundant perithecia were produced on rice straw, and 247 single-ascospore isolates were recovered from 247 perithecia. Perithecia representing lineage 6 (87%) were the most common, followed by those representing lineage 7 (13%), with perithecia representing lineage 3 not detected. These results suggest that F. graminearum lineage 6 may have a host preference for rice and that it may be more fit in a rice agroecosystem than are the other lineages present in Korea.


Subject(s)
Fusarium/classification , Fusarium/physiology , Genetic Variation , Oryza/microbiology , Trichothecenes/biosynthesis , Amplified Fragment Length Polymorphism Analysis , Cluster Analysis , DNA Fingerprinting , DNA, Fungal/genetics , Fusarium/genetics , Fusarium/isolation & purification , Genotype , Korea , Mycotoxins/biosynthesis
3.
Biol Pharm Bull ; 30(1): 21-6, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17202653

ABSTRACT

Minoxidil enhances hair growth by prolonging the anagen phase and induces new hair growth in androgenetic alopecia (AGA), whereas retinol significantly improves scalp skin condition and promotes hair growth. We investigated the combined effects of minoxidil and retinol on human hair growth in vitro and on cultured human dermal papilla cells (DPCs) and epidermal keratinocytes (HaCaT). The combination of minoxidil and retinol additively promoted hair growth in hair follicle organ cultures. In addition, minoxidil plus retinol more effectively elevated phosphorylated Erk, phosphorylated Akt levels, and the Bcl-2/Bax ratio than minoxidil alone in DPCs and HaCaT. We found that the significant hair shaft elongation demonstrated after minoxidil plus retinol treatment would depend on the dual kinetics associated with the activations of Erk- and Akt-dependent pathways and the prevention of apoptosis by increasing the Bcl-2/Bax ratio.


Subject(s)
Hair Follicle/drug effects , Hair/drug effects , Minoxidil/pharmacology , Skin/drug effects , Vitamin A/pharmacology , Vitamins/pharmacology , Adult , Alopecia/drug therapy , Apoptosis/drug effects , Cell Line , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Therapy, Combination , Extracellular Signal-Regulated MAP Kinases/metabolism , Hair/growth & development , Hair/metabolism , Hair Follicle/growth & development , Hair Follicle/metabolism , Humans , Keratinocytes/drug effects , Male , Minoxidil/therapeutic use , Organ Culture Techniques , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Skin/cytology , Skin/metabolism , Vitamin A/therapeutic use , Vitamins/therapeutic use , bcl-2-Associated X Protein/metabolism
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