{"id":8003,"date":"2020-10-18T13:48:52","date_gmt":"2020-10-18T10:48:52","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=8003"},"modified":"2020-12-20T14:28:04","modified_gmt":"2020-12-20T11:28:04","slug":"als-amyotrofik-lateral-skleroz","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/als-amyotrofik-lateral-skleroz\/","title":{"rendered":"ALS (Amyotrofik Lateral Skleroz)"},"content":{"rendered":"\n
\"\"
(Stephen Hawking. G\u00f6rsel Kayna\u011f\u0131: The World in HDR\/Shutterstock<\/a>)<\/figcaption><\/figure>\n\n\n\n

Giri\u015f<\/p>\n\n\n\n

Hepimizin asl\u0131nda \u00fcnl\u00fc fizik\u00e7i Stephen Hawking\u2019den a\u015fina oldu\u011fu Amyotrofik Lateral Skleroz (ALS), motor n\u00f6ronlar\u0131n hasar g\u00f6rmesi sonucu kaslar\u0131n g\u00fc\u00e7s\u00fcz d\u00fc\u015fmesidir. Bu nedenle di\u011fer ad\u0131 Motor N\u00f6ron Hastal\u0131\u011f\u0131\u2019d\u0131r [Motor Neuron Disease (MND)]. Hasta zaman ge\u00e7tik\u00e7e k\u00f6t\u00fcle\u015fir. \u00d6nce kol ve bacaklarda, sonra t\u00fcm v\u00fccutta hareket zorla\u015f\u0131r. En sonunda nefes alma, konu\u015fma ve yutma da g\u00fc\u00e7le\u015fir. Nadir bir hastal\u0131kt\u0131r ve bula\u015f\u0131c\u0131 de\u011fildir. Her y\u0131l 100 binde 2-6 ki\u015fide g\u00f6r\u00fcl\u00fcr. Net bir tedavisi yoktur, sadece hastal\u0131\u011f\u0131n ilerlemesi geciktirilir. Ortalama ya\u015fam \u00f6mr\u00fc hastal\u0131\u011f\u0131n ba\u015flang\u0131c\u0131ndan itibaren 4-6 y\u0131ld\u0131r. Ancak baz\u0131 hastalar 20 y\u0131l ya\u015fayabilir. N\u00f6rolojik hastal\u0131klar aras\u0131nda hasta ba\u015f\u0131na d\u00fc\u015fen maliyetin en y\u00fcksek oldu\u011fu hastal\u0131klardan biridir ve bu konuda sa\u011fl\u0131k kurulu\u015flar\u0131na b\u00fcy\u00fck sorumluluk d\u00fc\u015fmektedir. Her y\u0131l Amerika\u2019da 6000 ALS hastas\u0131 hayat\u0131n\u0131 kaybetmektedir. 2040\u2019larda ise d\u00fcnya genelinde yakla\u015f\u0131k 400 bin ki\u015finin bu hastal\u0131ktan hayat\u0131n\u0131 kaybedece\u011fi tahmin ediliyor. Bunun nedeni ise ya\u015fl\u0131 n\u00fcfusun artmas\u0131r. <\/p>\n\n\n\n

ALS \u00e7o\u011funlukla 40-60 ya\u015flar\u0131nda g\u00f6r\u00fcl\u00fcr ve hastalar\u0131n b\u00fcy\u00fck k\u0131sm\u0131 erkektir. Yo\u011fun fiziksel aktivite i\u00e7eren mesleklerde hastal\u0131\u011f\u0131n g\u00f6r\u00fclme olas\u0131l\u0131\u011f\u0131 daha y\u00fcksektir. Sigara i\u00e7enler de risk alt\u0131ndad\u0131r. <\/p>\n\n\n\n

\"\"
(ALS y\u00fcr\u00fcmede zorluk, tak\u0131l\u0131p d\u00fc\u015fme, el ve bacaklarda zay\u0131fl\u0131k, geveleme, bo\u011fulma ve kramplar ile ba\u015flar. Sonunda hasta ak\u00fcl\u00fc tekerlekli sandalyeye muhta\u00e7 olur. Hidrolik hasta kald\u0131rac\u0131na gereksinim duyar. Bunun sebebi motor n\u00f6ronlar\u0131n zay\u0131flamas\u0131 ve kaslar\u0131n atrofiye u\u011framas\u0131d\u0131r.)
(G\u00f6rsel Kayna\u011f\u0131: Leremy\/Shutterstock<\/a>, ID: 1312643564) <\/figcaption><\/figure>\n\n\n\n

Hastal\u0131\u011f\u0131n ba\u015flang\u0131c\u0131\nki\u015fiden ki\u015fiye de\u011fi\u015febilir. Genellikle kol ve bacaklarda kramp, sertlik ve\nse\u011firmelerle ba\u015flar ve bunu yutma ile konu\u015fma g\u00fc\u00e7l\u00fc\u011f\u00fc takip eder. \u0130lerleyen\nsafhalarda y\u00fcr\u00fcme bozuklu\u011fu, y\u00fcr\u00fcrken duraksama ve kalem ve bardak gibi\nnesneleri tutmada zorluk ya\u015fan\u0131r. Hastalar\u0131n %10\u2019unda da solunum, konu\u015fma ve\nyutmada kullan\u0131lan kaslar etkilenir. Son evrelerde kaslar \u00e7ok eridi\u011fi i\u00e7in\nhasta yata\u011fa d\u00fc\u015fer ve solunum cihaz\u0131na gereksinim duyar. Fakat zeka, haf\u0131za,\nba\u011f\u0131rsak, mesane, duyular ve kalp kas\u0131 etkilenmez. G\u00f6z kaslar\u0131 ya en son\netkilenir ya da hi\u00e7 etkilenmez. Kilo kayb\u0131, y\u00fcr\u00fcrken yere d\u00fc\u015fme, yorgunluk,\nengellenemeyen g\u00fclme ve a\u011flamalar da g\u00f6r\u00fcl\u00fcr. <\/p>\n\n\n\n

Tan\u0131 i\u00e7in ALS\u2019ye \u00f6zg\u00fc bir\ntest yoktur. Elektromiyografi (EMG), kan ve idrar testleri, tiroid fonksiyon\ntesti, kas ve sinir biyopsisi, r\u00f6ntgen, MR, lumbar ponksiyon (L3-4 vertebralar\naras\u0131ndan i\u011fneyle beyin-omurilik s\u0131v\u0131s\u0131n\u0131n al\u0131nmas\u0131) gibi bir\u00e7ok i\u015flem\nuygulan\u0131r. Hastal\u0131\u011f\u0131 ortadan kald\u0131racak bir tedavi yok ancak ya\u015fam kalitesini\nd\u00fczeltecek ve \u00f6mr\u00fc uzatacak tedaviler vard\u0131r. Semptomlar\u0131 azaltacak ila\u00e7lar,\nfizik tedavi, yeme g\u00fc\u00e7l\u00fc\u011f\u00fcnden dolay\u0131 ALS\u2019lere \u00f6zg\u00fc beslenme program\u0131, konu\u015fma\nterapisi; bilgisayar, solunum cihaz\u0131, haval\u0131 yatak, ak\u00fcl\u00fc tekerlekli sandalye,\nbeslenme t\u00fcp\u00fc gibi \u00e7e\u015fitli cihaz ve malzemelerle uyum tedavisi uygulan\u0131r. ALS\u2019nin\nsolunum cihaz\u0131n\u0131n ba\u011fland\u0131\u011f\u0131 son evresine kadar hasta kendine bakabilir. S\u00fcre\u00e7\nboyunca hastan\u0131n d\u00fczenli spor da yapmas\u0131 istenir. <\/p>\n\n\n\n

Genetik Ara\u015ft\u0131rmalar<\/p>\n\n\n\n

\u00c7e\u015fitli \u00e7al\u0131\u015fmalarda %90-95 kadar ALS hastas\u0131n\u0131n ailesinde bir hastal\u0131k ge\u00e7mi\u015fi bulunmam\u0131\u015ft\u0131r. Buna sporadik ALS (sALS) denir. Kalan %5-10\u2019luk kesiminse ailesinde ALS tespit edilmi\u015ftir. Buna da ailevi ALS (fALS) denir. Hastalar\u0131n \u00e7o\u011funun sALS olmas\u0131n\u0131n v\u00fccutta ger\u00e7ekle\u015fen \u00e7oklu reaksiyonlardan kaynakland\u0131\u011f\u0131 d\u00fc\u015f\u00fcn\u00fcl\u00fcyor. Bu reaksiyonlar geneti\u011fi de etkileyebilir. <\/p>\n\n\n\n

\"\"
(Normal ve ALS n\u00f6ron h\u00fccreleri. G\u00f6rsel Kayna\u011f\u0131: BlueRingMedia\/Shutterstock<\/a>)
<\/figcaption><\/figure>\n\n\n\n

\u0130lk defa 1993\u2019te Rosen et al. <\/em>taraf\u0131ndan ALS\u2019nin bir sebebi\nbulunmu\u015ftur. Bulduklar\u0131 s\u00fcperoksit dismutaz-1 (SOD1<\/em>)geni mutasyonudur\nve fALS\u2019lerin yakla\u015f\u0131k %20\u2019sinin, sALS\u2019lerin de yakla\u015f\u0131k %2\u2019sinin nedenidir. SOD1 <\/em>mutasyonu protein birikimine sebep\nolur. Bir\u00e7ok ALS\u2019li hayvan \u00fcst\u00fcnde yap\u0131lan \u00e7al\u0131\u015fmada SOD1 <\/em>geni mutasyonunun aksonal transport defektine yol a\u00e7t\u0131\u011f\u0131\ng\u00f6r\u00fclm\u00fc\u015ft\u00fcr. ALS\u2019nin bir di\u011fer nedeni KIF5A\n<\/em>geninin mutasyonudur. Ancak bu mutasyon kal\u0131tsal spastik parapleji (HSP) ve\nCharcot-Marie-Tooth\u2019ta (CMT) olan KIF5A <\/em>mutasyonundan\nfarkl\u0131d\u0131r. <\/p>\n\n\n\n

New York Genom Merkezi\u2019nin yapt\u0131\u011f\u0131 bir \u00e7al\u0131\u015fmada 148 ALS hastas\u0131n\u0131n korteksinden postmortem al\u0131nan \u00f6rnekler 3 gruba ayr\u0131lm\u0131\u015ft\u0131r. \u00d6rneklerin %61\u2019inde retrotranspozon aktivasyonu ve TARDBP<\/em> (TAR DNA Ba\u011flay\u0131c\u0131 Protein 43 \/ TDP-43<\/em>) geni disfonksiyonu, %19\u2019unda oksidatif stres ve %20\u2019sinde bask\u0131n olarak glia aktivasyonu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Retrotranspozon, RNA\u2019n\u0131n ters transkripsiyona u\u011frayarak DNA\u2019ya eklenmeye \u00e7al\u0131\u015fan \u015feklidir. TDP-43<\/em> proteini retrotranspozona ba\u011flanarak DNA\u2019ya eklenmesini ve b\u00f6ylece genomun de\u011fi\u015fmesini engeller. Ancak TDP-43<\/em> eksikli\u011finde retrotranspozonlar\u0131n say\u0131s\u0131 artar ve bu h\u00fccre geneti\u011fini olumsuz etkiler. <\/p>\n\n\n\n

Normal bir n\u00f6ron h\u00fccresinde TDP-43 proteini STMN-2\ngenindeki 2a b\u00f6lgesini inhibe ederek Stathmin-2 (STMN2) poteinini \u00fcretir.<\/p>\n\n\n\n

TDP-43 disfonksiyonu sonucu ALS bir hastan\u0131n n\u00f6ron \u00e7ekirde\u011finde TDP-43 eksikli\u011fi ve sitoplazmik TDP-43 agregatlar\u0131 g\u00f6zlenir. TDP-43 STMN2 genindeki 2a b\u00f6lgesini inhibe etmedi\u011fi i\u00e7in STMN2 proteini \u00fcretilmemektedir. Sonu\u00e7 olarak h\u00fccre par\u00e7alan\u0131r.<\/p>\n\n\n\n

\"\"
(Motor N\u00f6ron. G\u00f6rsel Kayna\u011f\u0131: grayjav\/Shutterstock<\/a>, ID:
1629602293) <\/figcaption><\/figure>\n\n\n\n

SOD1, C9ORF72, TDP-43 ve FUS genlerinde mutasyon\nsonucu n\u00f6ron h\u00fccresinde oksidatif stres ger\u00e7ekle\u015febilir. Mikroglialar\ninflamatuar arac\u0131 molek\u00fclleri salg\u0131lar ve astrositler hem h\u00fccre i\u00e7ine glutamat\nalamaz hem de toksik fakt\u00f6rler salg\u0131lar.<\/p>\n\n\n\n

Oksidatif stres, glial\naktivasyon, protein birikimi ve genetik bozukluklar d\u0131\u015f\u0131nda ER stresi,\nglutamaterjik sitotoksi, mitokondri bozukluklar\u0131 ve aksonal transport bozuklu\u011fu\nda ALS\u2019ye sebep olabilir. ALS\u2019ye 1950 ve 1960\u2019larda Japonya\u2019n\u0131n Kii\nyar\u0131madas\u0131nda di\u011fer \u00fclkelere k\u0131yasla 10 kat daha fazla rastlan\u0131yordu ancak \u015fu\nan di\u011fer \u00fclkelerle e\u015fit durumda. Bu kademeli d\u00fc\u015f\u00fc\u015f\u00fcn sebebiyse bilinmiyor. Bu\nb\u00f6lgenin \u00e7evresel \u00f6zellikleri incelendi\u011finde i\u00e7me suyundaki Kalsiyum ve \u00c7inko\u2019nun\ndi\u011fer b\u00f6lgelerdeki sulardan daha az oldu\u011fu saptanm\u0131\u015ft\u0131r. Buradaki ALS\nhastalar\u0131n\u0131n serumlar\u0131nda da Kalsiyum ve \u00c7inko d\u00fc\u015f\u00fckt\u00fcr. Sa\u00e7lar\u0131nda ise Mangan\nve Vanadyum miktar\u0131 fazlad\u0131r. \u0130drarlar\u0131nda daha \u00e7ok 8-hidroksi\n2\u2019-deoksiguanozin (8-OHdG<\/em>) tespit\nedilmi\u015ftir. Bu molek\u00fcl DNA oksidasyonunu g\u00f6sterir. Ayr\u0131ca bu bireylerde serum miRNA<\/em> tiplerinin miktar\u0131 da\nde\u011fi\u015fmektedir. ALS\u2019ye sebep olan di\u011fer genetik mutasyonlar C9ORF72<\/em>, FUS\/TLS<\/em>, OPTN\/FIP2<\/em>, TBK-1<\/em>, GRN<\/em>, NEK1<\/em> ve C21ORF2<\/em> mutasyonlar\u0131d\u0131r.<\/p>\n\n\n\n

Bilgi Kaynak\u00e7as\u0131<\/p>\n\n\n\n

  1. Ac\u0131badem. Ac\u0131badem Web ve Yay\u0131n Kurulu. 28.08.2019. https:\/\/www.acibadem.com.tr\/ilgi-alani\/als-amyotrofik-lateral-skleroz\/<\/a> <\/li>
  2. ScienceDirect. Tam et al., 2019, Cell Reports 29, 1164\u20131177,\nOctober 29, 2019 \u00aa 2019 The Author(s).  https:\/\/doi.org\/10.1016\/j.celrep.2019.09.066<\/a>  <\/li>
  3. ScienceDirect. Arakawa et al., Association between oxidative stress\nand microRNA expression pattern of ALS patients in the high-incidence area of\nthe Kii Peninsula, Brain Research, <\/em>1746\n(2020).  <\/li>
  4. ScienceDirect. Nicolas et al., Genome-wide Analyses Identify KIF5A\nas a Novel ALS Gene, Neuron <\/em>(97):6,\n1268-1283.e6 (2020). <\/li>
  5. NCBI. Geon Chung, Chang. Lee, Hyosang. Bae Lee, Sung., Mechanisms\nof protein toxicity in neurodegenerative diseases, Cellular and Molecular Life Sciences<\/em> 75:(17), 3159-3180 (2018). <\/li><\/ol>\n\n\n\n

    G\u00f6rsel Kaynak\u00e7as\u0131<\/p>\n\n\n\n

    1. The World in HDR\/Shutterstock<\/a> <\/li>
    2. Leremy\/Shutterstock<\/a>, ID: 1312643564 <\/li>
    3. BlueRingMedia\/Shutterstock<\/a> <\/li>
    4. grayjav\/Shutterstock<\/a>, ID: 1629602293 <\/li><\/ol>\n\n\n\n

      <\/p>\n\n\n\n

      <\/p>\n","protected":false},"excerpt":{"rendered":"

      Giri\u015f Hepimizin asl\u0131nda \u00fcnl\u00fc fizik\u00e7i Stephen Hawking\u2019den a\u015fina oldu\u011fu Amyotrofik Lateral Skleroz (ALS), motor n\u00f6ronlar\u0131n hasar g\u00f6rmesi sonucu kaslar\u0131n g\u00fc\u00e7s\u00fcz<\/p>\n","protected":false},"author":267,"featured_media":8013,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1,25],"tags":[708,1244,941,994,1206,1263,95,194,74,894,893,1220,1257,1250,942,1252,1231,274,1235,1260,1210,1261,149,481,1228,543,115,810,1187,1239,1247,1255,990,92,1090,1245,1251,1211,514,1227,1221,1237,1216,76,1253,1240,485,1248,1241,1249,956,1213,1214,1256,1232,220,1238,297,1259,996,1229,1243,1233,160,1217,1215,1225,1222,1230,1224,1242,1207,1246,1208,1219,1234,1258,1226,84,1223,374,1218,1262,1236,1254,1212],"acf":[],"views":1605,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/8003"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/267"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=8003"}],"version-history":[{"count":7,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/8003\/revisions"}],"predecessor-version":[{"id":9174,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/8003\/revisions\/9174"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/8013"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=8003"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=8003"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=8003"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}