Molecular Genetics of Alopecias

Ramot, Yuval; Zlotogorski, Abraham

doi:10.1159/000369408

Cited by 9 publications

(5 citation statements)

References 77 publications

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“…Furthermore, N 1 -methylspermidine can exert anti-oxidative and anti-inflammatory effects on human cells in vitro [ 20 ], which are both relevant to the human HF growth and function. Polyamines, and among them spermidine, might also be linked to the hairless protein [ 28 , 29 ], which has an important role in controlling normal hair function and cycle [ 20 , 31 ]. The fact that spermidine was found to enhance longevity supports the anagen-promoting effects observed in this study, as the duration of anagen is a good indicator for the HF vitality [ 32 – 34 ].…”

Section: Discussionmentioning

confidence: 99%

A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study

Rinaldi

Mora

Pinto

et al. 2017

Dermatol Pract Concept

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BackgroundSpermidine has been shown both in vitro and in mice models to have an anagen-prolonging effect on hair follicles (HFs).ObjectivesTo evaluate the effects of a spermidine-based nutritional supplement on the anagen phase of HFs in healthy human subjects in a randomized, double-blind, placebo-controlled trial.MethodsOne hundred healthy males and females were randomized to receive a tablet containing a spermidine-based nutritional supplement or a placebo once daily for 90 days. At the beginning and the end of the treatment period, 100 HFs were plucked and subjected to microscopic evaluation to determine the number of anagen V–VI HFs, and immunohistochemical examination was performed to quantify the Ki-67 and c-Kit levels in the hair bulbs. Pull test was performed after three and six months.ResultsThe spermidine-based nutritional supplement increased the number of anagen V–VI HFs after three months of treatment, accompanied by increased Ki-67, a marker for cellular proliferation, and decreased c-Kit, a marker for apoptosis, levels. All results were also significantly better when compared to the placebo group. The pull test remained negative after six months in all patients receiving the spermidine supplement, while 68% of the subjects in the placebo group had a positive pull test.ConclusionsThis preliminary study shows that a spermidine-based nutritional supplement can prolong the anagen phase in humans, and therefore might be beneficial for hair loss conditions. Further studies are needed to evaluate its effects in specific different clinical settings.

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Section: Discussionmentioning

confidence: 99%

A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study

Rinaldi

Mora

Pinto

et al. 2017

Dermatol Pract Concept

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“…This questions whether genetic risk factors are as critical to the induction of AA as is often proclaimed [25,33,110,111], and also whether all forms of human AA require the presence of preexisting autoreactive CD8+ T cells that recognize an MHC class I-presented autoantigen [12,20]. Therefore, it has already been proposed that AA may best be viewed as a stereotypic HF response pattern to a spectrum of diverse inflammation-related damaging events, that all share the induction of IP collapse and HF dystrophy in the anagen hair bulb, resulting in the AA hair phenotype [5].…”

Section: Murine Models Of Aamentioning

confidence: 99%

Alopecia areata: Animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies

Gilhar

Schrum

Etzioni³

et al. 2016

Autoimmunity Reviews

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One of the most common human autoimmune diseases, alopecia areata (AA), is characterized by sudden, often persisting and psychologically devastating hair loss. Animal models have helped greatly to elucidate critical cellular and molecular immune pathways in AA. The two most prominent ones are inbred C3H/HeJ mice which develop an AA-like hair phenotype spontaneously or after experimental induction, and healthy human scalp skin xenotransplanted onto SCID mice, in which a phenocopy of human AA is induced by injecting IL-2-stimulated PBMCs enriched for CD56+/NKG2D+ cells intradermally. The current review critically examines the pros and cons of the available AA animal models and how they have shaped our understanding of AA pathobiology, and the development of new therapeutic strategies. AA is thought to arise when the hair follicle’s (HF) natural immune privilege (IP) collapses, inducing ectopic MHC class I expression in the HF epithelium and autoantigen presentation to autoreactive CD8+ T cells. In common with other autoimmune diseases, upregulation of IFN-γ and IL-15 is critically implicated in AA pathogenesis, as are NKG2D and its ligands, MICA, and ULBP3. The C3H/HeJ mouse model was used to identify key immune cell and molecular principles in murine AA, and proof-of-principle that Janus kinase (JAK) inhibitors are suitable agents for AA management in vivo, since both IFN-γ and IL-15 signal via the JAK pathway. Instead, the humanized mouse model of AA has been used to demonstrate the previously hypothesized key role of CD8+ T cells and NKG2D+ cells in AA pathogenesis and to discover human-specific pharmacologic targets like the potassium channel Kv1.3, and to show that the PDE4 inhibitor, apremilast, inhibits AA development in human skin. As such, AA provides a model disease, in which to contemplate general challenges, opportunities, and limitations one faces when selecting appropriate animal models in preclinical research for human autoimmune diseases.

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“…). A high number of other genes in humans and rodents have been implicated in abnormal hair development and hypotrichosis (Shimomura & Christiano ; Ramot & Zlotogorski ), making it impractical to use a candidate gene approach to successfully identify polymorphisms associated with the hairless phenotype in pig populations.…”

Section: List Of Significant (Pmentioning

confidence: 99%

Taking advantage from phenotype variability in a local animal genetic resource: identification of genomic regions associated with the hairless phenotype in Casertana pigs

et al. 2018

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Casertana is an endangered autochthonous pig breed (raised in south-central Italy) that is considered to be the descendant of the influential Neapolitan pig population that was used to improve British breeds in the 19th century. Casertana pigs are characterized by a typical, almost complete, hairless phenotype, even though a few Casertana pigs are normal haired. In this work, using Illumina PorcineSNP60 BeadChip data, we carried out a genome-wide association study and an F analysis with this breed by comparing animals showing the classical hairless phenotype (n = 81) versus pigs classified as haired (n = 15). Combining the results obtained with the two approaches, we identified two significant regions: one on porcine chromosome (SSC) 7 and one on SSC15. The SSC7 region contains the forkhead box N3 (FOXN3) gene, the most plausible candidate gene of this region, considering that mutations in another gene of the same family (forkhead box N1; Foxn1 or FOXN1) are responsible for the nude locus in rodents and alopecia in humans. Another potential candidate gene, rho guanine nucleotide exchange factor 10 (ARHGEF10), is located in the SSC15 region. FOXN3 and ARHGEF10 have been detected as differentially expressed in androgenetic and senescent alopecia respectively. This study on an autochthonous pig breed contributes to shed some light on novel genes potentially involved in hair development and growth and demonstrates that local animal breeds can be valuable genetic resources for disclosing genetic factors affecting unique traits, taking advantage of phenotype variability segregating in small populations.

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Molecular Genetics of Alopecias

Cited by 9 publications

References 77 publications

A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study

A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study

Alopecia areata: Animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies

Taking advantage from phenotype variability in a local animal genetic resource: identification of genomic regions associated with the hairless phenotype in Casertana pigs

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