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Gerontology & Geriatrics

Commentary Volume 3 Issue 1

Tight junction protein 1 gene in neurodegenerative disease, new frontier

Mar a E Aguilar Aldrete,1 Perla M MadrigalRuiz,2 Luis Javier FloresAlvarado,2 Rosalba Ruiz Mejia,2 Felipe Parada Luna,3 Sergio Alberto Ramirez Garcia4

1Department of Public Health and Psicogeriatric College, University Center of Health Sciences, Mexico
2Laboratory of Biochemistry, Department of Molecular Biology and Genomics, University Center of Health Sciences, Mexico
3Program of Health Public Master, University of the Sierra Sur, Mexico
4Institute of Public Health Research, University of the Sierra Sur, Mexico

Correspondence: Sergio Alberto Ramirez Garcia, Masters program in public health, Universidad Col & Ciudad Universitaria, Miahuatl, Tel 01(376) 76 5-23-25

Received: August 24, 2017 | Published: January 25, 2018

Citation: Aldrete MEA, MadrigalRuiz PM, Alvarado LJF, et al. Tight junction protein 1 gene in neurodegenerative disease, new frontier. MOJ Gerontol Ger. 2018;3(1):51-52 DOI: 10.15406/mojgg.2018.03.00084

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Introduction

The older adults are a consequence of the aging process and may be susceptible to the development of metabolic diseases related to atherosclerosis such as vascular dementias, cerebrovascular disease, or neurodegenerative diseases such as essential tremor, Parkinson plus syndromes, Parkinson's disease. Prevention, diagnosis and biomonitoring require the search for new genetic markers that are predictive of their clinical evolution or response to treatment. One of the candidate genes for these purposes is the Tight Junction Protein 1 (TJP1) gene, which codes for the Zonna occludens 1 (ZO-1). It has stayed than tight junctions than constitute the blood-brain barrier which controls the intracellular diffusion and maintains the functional structural of endothelial cells. Structure or function of tight junctions can lead to the blood-brain barrier dysfunction that consequently may contribute to the development of neurological diseases1. Blood-brain barrier disruption, associated with alterations of tight junctions, has been implicated in the pathogenesis of neurodegenerative disorders including multiple sclerosis, stroke, Alzheimer’s and Parkinson’s disease.1 In this sense, genetic marker of the gene that leads to amino acid changes, such as polymorphism rs229166 leads to a conformational change in the ZO-1 structure.2 Some of those polymorphisms that lead to amino acid changes in critical domains of the protein are rs1038306187 leading to the change of amino acid p.Gln791Glu in the domain guanylate kinase (Location residue 682-861). The domain ZU5 (Location residue 1701-1799) has 33 polymorphisms leading to conformational changes (Table 1). Polymorphisms that affect gene expression, by nucleotide changes at the cryptic sites of the alternative splicing, such as rs781148827, rs5478300017, rs78014403 and rs1020739943 in acceptor region, and rs1029122894 in the donor region. None of these polymorphisms have been explored for their pathogenic effect, which is why they are a new frontier of research in neurodegenerative disease related to aging, due to their effect on ZO-1 expression.

Number SNP

Reference

Nucleotide Change

Protein Change

Protein Residue

Number SNP

Reference

Nucleotide Change

Protein Change

Protein Residue

rs756391449

missense

T

Val [V]

1786

rs200636289

missense

A

Lys [K]

1732

contig reference

C

Ala [A]

1786

contig reference

G

Glu [E]

1732

rs778206679

missense

T

Cys [C]

1781

rs780493261

missense

A

Thr [T]

1729

contig reference

C

Arg [R]

1781

contig reference

G

Ala [A]

1729

rs376984007

missense

T

Ser [S]

1777

rs747547138

missense

A

Arg [R]

1728

contig reference

C

Pro [P]

1777

contig reference

G

Gly [G]

1728

rs771212279

missense

T

Asn [N]

1773

rs777243709

missense

G

Met [M]

1723

contig reference

G

Lys [K]

1773

contig reference

A

Ile [I]

1723

rs779424333

missense

G

Val [V]

1772

rs748887539

missense

G

Val [V]

1723

missense contig

T

Phe [F]

1772

contig reference

A

Ile [I]

1723

contig reference

C

Leu [L]

1772

rs770484844

missense

A

Asn [N]

1722

rs918494224

missense

A

Asp [D]

1771

contig reference

G

Ser [S]

1722

contig reference

G

Gly [G]

1771

rs748606073

missense

A

Ile [I]

1721

rs769318736

missense

G

Glu [E]

1754

contig reference

G

Val [V]

1721

contig reference

A

Lys [K]

1754

rs745589986

missense

C

Gln [Q]

1718

rs772813539

missense

C

Ser [S]

1752

contig reference

G

Glu [E]

1718

contig reference

T

Leu [L]

1752

rs772012909

missense

C

Thr [T]

1717

rs748862082

missense

G

Val [V]

1749

contig reference

T

Ile [I]

1717

contig reference

C

Leu [L]

1749

rs775526130

missense

A

Met [M]

1713

rs770667262

missense

A

Asn [N]

1747

contig reference

G

Val [V]

1713

contig reference

G

Ser [S]

1747

rs776556981

missense

A

Asp[D]

1712

rs55855417

contig reference

A

Asn [N]

1745

contig reference

G

Gly [G]

1712

missense

G

Asp [D]

1745

rs200635441

missense

G

Lys [K]

1710

rs759442574

contig reference

A

Gln[Q]

1744

contig reference

T

Asn [N]

1710

missense

G

Arg [R]

1744

rs200271901

missense

G

Ser [S]

1710

rs578134163

contig reference

G

Arg [R]

1741

contig reference

A

Asn [N]

1710

missense

A

Lys [K]

1741

rs750682659

missense

A

Lys [K]

1706

rs976771573

contig reference

G

Glu [E]

1741

contig reference

T

Ile [I]

1706

missense

A

Lys [K]

1741

rs758653969

missense

A

Asp[D]

1705

Table 1 Polymorphisms in the TJP1 en region encoding by the ZU5 domain.

There are few polymorphism studies of the ZO-1 gene in the world. It has been studied in Mexican Americans with a pathogenic effect on albuminuria such as rs2291166.3 Or Also in the Mexican population with Mestiza and Zapoteca ancestry has been determinate its allelic frequencies.2,4 The SNP rs260526 related with inflammatory bowel disease or the SNP.5 Or SNP rs711355, rs785423, rs813676 associated with global impression severity during risperidone treatment.6 So its effect on the development of neurodegenerative diseases in the older adult is another of the research frontiers.

Finally it would be important to analyze the interaction of the SNP commented on TJP1 with the SNP rs767649 of miR-1557 which regulates the expression of TJP1, a field not well known in the development of neurodegenerative diseases related to aging, one of the most important borders at the level epigenetic and epistasia.

Acknowledgements

None.

Conflict of interest

Authors declare that there are no conflicts of interest.

References

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©2018 Aldrete, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.