Transplantation of Melanocytes Obtained from the Skin Ameliorates Apomorphine-Induced Abnormal Behavior in Rodent Hemi-Parkinsonian Models

Asanuma, Masato; Miyazaki, Ikuko; Díaz-Corrales, Francisco J.; Higashi, Youichirou; Namba, Masayoshi; Ogawa, Norio

doi:10.1371/journal.pone.0065983

Cited by 8 publications

(5 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent report studying α‐syn behavior in SK‐MEL‐28 proposes that the transfer of α‐syn from melanoma to neuronal cells may affect the pathogenesis of PD (Lee et al 2013a). Interestingly, the transplantation of tyrosinase‐positive melanocytes in rat models of PD has been shown to have beneficial effects and further argues for the need to explore α‐syn behavior in melanoma (Asanuma et al 2013). The presence of higher molecular weight species of α‐syn in SK‐MEL‐28 and the differential localization of the two forms of α‐syn makes SK‐MEL‐28 a good model to evaluate the formation and existence of non‐toxic oligomers and to investigate if these higher order structures have any physiological significance under normal cellular conditions.…”

Section: Discussionmentioning

confidence: 99%

Autophagy enhancement is rendered ineffective in presence of α-synuclein in melanoma cells

Nandakumar

Vijayan

Kishore

et al. 2017

J. Cell Commun. Signal.

View full text Add to dashboard Cite

Increased cellular concentration of α-synuclein (α-syn) predisposes it to misfolding and aggregation that in turn impair the degradation pathways. This poses a limitation to the use of overexpression models for studies on α-syn clearance by autophagy, which is widely investigated for its therapeutic potential. This limitation can be overcome with the use of endogenous models. In this study, SK-MEL-28, a melanoma cell model with endogenous α-syn expression, was employed to study α-syn clearance through autophagy. We demonstrated the dual localization of α-syn to nucleus and cytoplasm that varied in response to changes in cellular environment. Autophagy inhibition and exposure to dopamine favored cytoplasmic localization of α-syn, while autophagy induction favored increased localization to the nucleus. The inhibitory effect of dopamine on autophagy was heightened in presence of α-syn. Additionally, because α-syn had a regulatory effect on autophagy, cells showed an increased resistance to autophagy induction in presence of α-syn. This resistance prevented effective induction of autophagy even under conditions of prolonged autophagy inhibition. These results highlight alternate physiological roles of α-syn, particularly in non-neuronal cells. Because autophagy enhancement could reverse neither the increase in α-syn levels nor the autophagy inhibition, there arises a need to evaluate the efficacy of autophagy-based therapeutic strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Autophagy enhancement is rendered ineffective in presence of α-synuclein in melanoma cells

Nandakumar

Vijayan

Kishore

et al. 2017

J. Cell Commun. Signal.

View full text Add to dashboard Cite

show abstract

“…6) Tyrosine hydroxylase : Vitiligo is a frequent autoimmune disease characterized by an immune-mediated destruction of melanocytes leading to skin depigmentation 114 . Interestingly, the biochemical pathways allowing the synthesis of melanin and dopamine respectively present major similarities 115 , 116 , and the intra-CNS grafting of melanocytes was recently proposed as a therapeutic approach for Parkinson's disease, a neurodegenerative disorder affecting dopaminergic neurons 115 . In this regard, tyrosine hydroxylase, a major enzyme of the dopamine synthesis pathway in neurons is also essential to melanin synthesis and is targeted by autoantibodies in vitiligo 117 , 118 .…”

Section: The Cns Is a Major Source Of Superautoantigensmentioning

confidence: 99%

Evolution, immunity and the emergence of brain superautoantigens

Nataf¹

2017

F1000Res

View full text Add to dashboard Cite

While some autoimmune disorders remain extremely rare, others largely predominate the epidemiology of human autoimmunity. Notably, these include psoriasis, diabetes, vitiligo, thyroiditis, rheumatoid arthritis and multiple sclerosis. Thus, despite the quasi-infinite number of "self" antigens that could theoretically trigger autoimmune responses, only a limited set of antigens, referred here as superautoantigens, induce pathogenic adaptive responses. Several lines of evidence reviewed in this paper indicate that, irrespective of the targeted organ (e.g. thyroid, pancreas, joints, brain or skin), a significant proportion of superautoantigens are highly expressed in the synaptic compartment of the central nervous system (CNS). Such an observation applies notably for GAD65, AchR, ribonucleoproteins, heat shock proteins, collagen IV, laminin, tyrosine hydroxylase and the acetylcholinesterase domain of thyroglobulin. It is also argued that cognitive alterations have been described in a number of autoimmune disorders, including psoriasis, rheumatoid arthritis, lupus, Crohn's disease and autoimmune thyroiditis. Finally, the present paper points out that a great majority of the "incidental" autoimmune conditions notably triggered by neoplasms, vaccinations or microbial infections are targeting the synaptic or myelin compartments. On this basis, the concept of an immunological homunculus, proposed by Irun Cohen more than 25 years ago, is extended here in a model where physiological autoimmunity against brain superautoantigens confers both: i) a crucial evolutionary-determined advantage via cognition-promoting autoimmunity; and ii) a major evolutionary-determined vulnerability, leading to the emergence of autoimmune disorders in Homo sapiens. Moreover, in this theoretical framework, the so called co-development/co-evolution model, both the development (at the scale of an individual) and evolution (at the scale of species) of the antibody and T-cell repertoires are coupled to those of the neural repertoires (i.e. the distinct neuronal populations and synaptic circuits supporting cognitive and sensorimotor functions). Clinical implications and future experimental insights are also presented and discussed.

show abstract

“…In fact, supplement of DA synthesis by tyrosinase has been reported in TH (Tyrosine Hydroxylase) null mice [14]. Further, it was shown earlier by [15] that transplantation of a non-melanogenic cells transfected with tyrosinase gene, as tyrosinase-producing cells, which constitutively produce L-DOPA, resulted in marked amelioration of the asymmetric apomorphine-induced rotation in hemi-parkinsonian mice lesioned with 6-hydroxydopamine (6-OHDA). In an another experiment they have also shown that transplantation of melanocytes from the back skin of black newborn mice, but not from albino mice, showed marked improvement in the apomorphine-induced rotation behavior.…”

Section: Discussionmentioning

confidence: 97%

“…Currently, the most common therapy uses the drug levodopa, a substrate of dopamine (DA) which is associated with motor skills [31]. Since melanocytes contain Tyrosinase which can synthesize DOPA from Tyrosine, it appears that transplantation of melanocytes can be a better substitute for DOPA therapy than Levodopa administration for PD patients [15]. Levodopa administration to PD patients while a continuous treatment and a palliative, transplantation of melanocytes could be onetime and the cells will supply DOPA regularly as when needed.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Selection of Cells for Parkinson's Disease Cell-Therapy

Ashok¹,

Anil²

2019

Int J Stem Cell Res Ther

View full text Add to dashboard Cite

Availability of DOPA in situ and thereafter Dopamine (DA) is the main therapeutic approach to treat the Parkinson's Disease (PD). Human neural stem cells (hNSCs), a good source of DA synthesis and release, have long been demonstrated to be a promising candidate for treating PD. However limited cell sourcing and low-growth rate are major concern of its applicability. Different types of other stem cells or reprogrammed somatic cells, including induced pluripotent stem cells (iPSCs), holds tremendous potentiality for DA synthesis and the treatment of Parkinson's disease (PD). However, several issues like ethical, tumor formation, genetic instability, are undermining their therapeutic application. Further the processes are laborious, time-consuming, and not cost-effective. Here, we compare the potentiality and applicability of using another DOPA-forming, neural crest originated cells, Melanocytes with hNSCs for the possible treatment of PD patients.

show abstract

Transplantation of Melanocytes Obtained from the Skin Ameliorates Apomorphine-Induced Abnormal Behavior in Rodent Hemi-Parkinsonian Models

Cited by 8 publications

References 25 publications

Autophagy enhancement is rendered ineffective in presence of α-synuclein in melanoma cells

Autophagy enhancement is rendered ineffective in presence of α-synuclein in melanoma cells

Evolution, immunity and the emergence of brain superautoantigens

Selection of Cells for Parkinson's Disease Cell-Therapy

Contact Info

Product

Resources

About