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'''Filamen PH''' ({{lang-en|neurofibrillary tangle, paired helical filaments, PHF}}) adalah tumpukan [[protein]] yang ditemukan pertama kali oleh [[Alois Alzheimer]] di dalam [[neuron]] penderita [[Alzheimer]].<ref>{{Cite web|last=alzi|date=2019-06-15|title=Apa yang menyebabkan demensia?|url=https://alzi.or.id/apa-yang-menyebabkan-demensia/|website=Alzheimer Indonesia|language=en|access-date=2024-09-28}}</ref>
[[Berkas:TAU_HIGH.JPG|thumb|right|150px|Protein Tau yang mengalami hiperfosforilasi menjadi filamen tak larut]]
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'''Filamen PH''' ({{lang-en|neurofibrillary tangle, paired helical filaments, PHF}}) adalah tumpukan [[protein]] yang ditemukan pertama kali oleh [[Alois Alzheimer]] di dalam [[neuron]] penderita [[Alzheimer]].


Filamen ini terbentuk dari berbagai [[isomer]]<ref>{{en}}{{cite web
Filamen ini terbentuk dari berbagai [[isomer]]<ref>{{en}} {{cite web
| url = http://www.ncbi.nlm.nih.gov/pubmed/2484340
| url = http://www.ncbi.nlm.nih.gov/pubmed/2484340
| title = Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease
| title = Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease
| accessdate = 2010-06-27
| accessdate = 2010-06-27
| work = Medical Research Council, Laboratory of Molecular Biology, Cambridge, England; Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA.
| work = Medical Research Council, Laboratory of Molecular Biology, Cambridge, England; Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA.
| archive-date = 2019-12-15
⚫
}}</ref> [[protein tau]]<ref>{{en}}{{cite web
| archive-url = https://web.archive.org/web/20191215025836/https://www.ncbi.nlm.nih.gov/pubmed/2484340
| dead-url = no
⚫
}}</ref> [[protein tau]]<ref>{{en}} {{cite web
| url = http://www.ncbi.nlm.nih.gov/pubmed/3131773
| url = http://www.ncbi.nlm.nih.gov/pubmed/3131773
| title = Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau
| title = Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau
| accessdate = 2010-06-27
| accessdate = 2010-06-27
| work = Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom; Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A.
| work = Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom; Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A.
| archive-date = 2019-04-01
⚫
}}</ref> - sebuah [[protein]] yang berperan dalam perakitan dan pemeliharaan struktur [[mikrotubula]] - mengalami [[hiperfosforilasi]] sehingga memecahkan struktur [[mikrotubula]]. Radikal protein tau kemudian berhimpun menjadi filamen PH di dalam [[soma]].<ref name="PM20553310">{{en}}{{cite web
| archive-url = https://web.archive.org/web/20190401194515/https://www.ncbi.nlm.nih.gov/pubmed/3131773
| dead-url = no
⚫
}}</ref> - sebuah [[protein]] yang berperan dalam perakitan dan pemeliharaan struktur [[mikrotubula]] - mengalami [[hiperfosforilasi]] sehingga memecahkan struktur [[mikrotubula]]. Radikal protein tau kemudian berhimpun menjadi filamen PH di dalam [[soma]].<ref name="PM20553310">{{en}} {{cite web
| url = http://www.ncbi.nlm.nih.gov/pubmed/20553310
| url = http://www.ncbi.nlm.nih.gov/pubmed/20553310
| title = The Role of Tau in Alzheimer's Disease and Related Disorders
| title = The Role of Tau in Alzheimer's Disease and Related Disorders
| accessdate = 2010-06-21
| accessdate = 2010-06-21
| work = Department of Neurobiology and Behavior and Institute for Memory Impairments and Neurological Disorders, University of California; Medeiros R, Baglietto-Vargas D, Laferla FM.
| work = Department of Neurobiology and Behavior and Institute for Memory Impairments and Neurological Disorders, University of California; Medeiros R, Baglietto-Vargas D, Laferla FM.
| archive-date = 2019-12-25
| archive-url = https://web.archive.org/web/20191225004208/https://www.ncbi.nlm.nih.gov/pubmed/20553310
| dead-url = no
}}</ref>
}}</ref>


Hiperfosforilasi terjadi karena terjadi kerusakan transduksi sinyal selular yang disebabkan oleh tidak seimbangnya aktivitas [[protein]] dari beberapa [[enzim]] [[fosfatase]] dan [[kinase]],<ref name="PM20553310" /> seperti ''calmodulin-dependent protein kinase II'', ''glycogen synthase kinase-3beta'' dan ''cyclin-dependent protein kinase 5''.<ref>{{en}}{{cite web
Hiperfosforilasi terjadi karena terjadi kerusakan transduksi sinyal seluler yang disebabkan oleh tid ak seimbangnya aktivitas [[protein]] dari beberapa [[enzim]] [[fosfatase]] dan [[kinase]],<ref name="PM20553310" /> seperti ''calmodulin-dependent protein kinase II'', ''[[glycogen synthase kinase-3beta]]'' dan ''cyclin-dependent protein kinase 5''.<ref>{{en}} {{cite web
| url = http://www.ncbi.nlm.nih.gov/pubmed/18194444
| url = http://www.ncbi.nlm.nih.gov/pubmed/18194444
| title = Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention
| title = Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention
| accessdate = 2010-06-21
| accessdate = 2010-06-21
| work = Department of Neurochemistry New York State Institute for Basic Research in Developmental Disabilities; Iqbal K, Grundke-Iqbal I.
| work = Department of Neurochemistry New York State Institute for Basic Research in Developmental Disabilities; Iqbal K, Grundke-Iqbal I.
| archive-date = 2016-06-11
⚫
}}</ref><ref>{{en}}{{cite web
| archive-url = https://web.archive.org/web/20160611142209/http://www.ncbi.nlm.nih.gov/pubmed/18194444
| dead-url = no
⚫
}}</ref><ref>{{en}} {{cite web
| url = http://www.ncbi.nlm.nih.gov/pubmed/17241267
| url = http://www.ncbi.nlm.nih.gov/pubmed/17241267
| title = Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration
| title = Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration
| accessdate = 2010-06-21
| accessdate = 2010-06-21
| work = Pathophysiology Department, Tongji Medical College, Huazhong University of Science & Technology; Wang JZ, Grundke-Iqbal I, Iqbal K.
| work = Pathophysiology Department, Tongji Medical College, Huazhong University of Science & Technology; Wang JZ, Grundke-Iqbal I, Iqbal K.
| archive-date = 2017-07-15
⚫
}}</ref> Proses kimiawi ini dapat diredam dengan meningkatkan aktivitas [[enzim]] [[fosfoseril protein fosfatase]]<ref>{{en}}{{cite web
| archive-url = https://web.archive.org/web/20170715052648/https://www.ncbi.nlm.nih.gov/pubmed/17241267
| dead-url = no
⚫
}}</ref> Proses kimiawi ini dapat diredam dengan meningkatkan aktivitas [[enzim]] [[fosfoseril protein fosfatase]]<ref>{{en}} {{cite web
| url = http://www.ncbi.nlm.nih.gov/pubmed/15270196
| url = http://www.ncbi.nlm.nih.gov/pubmed/15270196
| title = Inhibition of neurofibrillary degeneration: a promising approach to Alzheimer's disease and other tauopathies
| title = Inhibition of neurofibrillary degeneration: a promising approach to Alzheimer's disease and other tauopathies
| accessdate = 2010-06-21
| accessdate = 2010-06-21
| work = Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities; Iqbal K, Grundke-Iqbal I.
| work = Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities; Iqbal K, Grundke-Iqbal I.
| archive-date = 2023-07-21
⚫
}}</ref> dan [[fosfotreonil protein fosfatase]].<ref>{{en}}{{cite web
| archive-url = https://web.archive.org/web/20230721053109/https://pubmed.ncbi.nlm.nih.gov/15270196/
| dead-url = no
⚫
}}</ref> dan [[fosfotreonil protein fosfatase]].<ref>{{en}} {{cite web
| url = http://www.ncbi.nlm.nih.gov/pubmed/10961432
| url = http://www.ncbi.nlm.nih.gov/pubmed/10961432
| title = Mechanism of neurofibrillary degeneration and pharmacologic therapeutic approach
| title = Mechanism of neurofibrillary degeneration and pharmacologic therapeutic approach
| accessdate = 2010-06-21
| accessdate = 2010-06-21
| work = New York State Institute for Basic Research in Developmental Disabilities; Iqbal K, Alonso AD, Gondal JA, Gong CX, Haque N, Khatoon S, Sengupta A, Wang JZ, Grundke-Iqbal I.
| work = New York State Institute for Basic Research in Developmental Disabilities; Iqbal K, Alonso AD, Gondal JA, Gong CX, Haque N, Khatoon S, Sengupta A, Wang JZ, Grundke-Iqbal I.
| archive-date = 2019-04-10
| archive-url = https://web.archive.org/web/20190410171022/https://www.ncbi.nlm.nih.gov/pubmed/10961432
| dead-url = no
}}</ref>
}}</ref>


Revisi terkini sejak 5 Januari 2025 05.55

Filamen PH (bahasa Inggris: neurofibrillary tangle, paired helical filaments, PHF) adalah tumpukan protein yang ditemukan pertama kali oleh Alois Alzheimer di dalam neuron penderita Alzheimer.[1]

Filamen ini terbentuk dari berbagai isomer[2] protein tau[3] - sebuah protein yang berperan dalam perakitan dan pemeliharaan struktur mikrotubula - mengalami hiperfosforilasi sehingga memecahkan struktur mikrotubula. Radikal protein tau kemudian berhimpun menjadi filamen PH di dalam soma.[4]

Hiperfosforilasi terjadi karena terjadi kerusakan transduksi sinyal seluler yang disebabkan oleh tid ak seimbangnya aktivitas protein dari beberapa enzim fosfatase dan kinase,[4] seperti calmodulin-dependent protein kinase II, glycogen synthase kinase-3beta dan cyclin-dependent protein kinase 5.[5][6] Proses kimiawi ini dapat diredam dengan meningkatkan aktivitas enzim fosfoseril protein fosfatase[7] dan fosfotreonil protein fosfatase.[8]

Rujukan

[sunting | sunting sumber]
  1. ^ alzi (2019-06-15). "Apa yang menyebabkan demensia?". Alzheimer Indonesia (dalam bahasa Inggris). Diakses tanggal 2024-09-28. 
  2. ^ (Inggris) "Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease". Medical Research Council, Laboratory of Molecular Biology, Cambridge, England; Goedert M, Spillantini MG, Jakes R, Rutherford D, Crowther RA. Diarsipkan dari versi asli tanggal 2019-12-15. Diakses tanggal 2010-06-27. 
  3. ^ (Inggris) "Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau". Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom; Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A. Diarsipkan dari versi asli tanggal 2019-04-01. Diakses tanggal 2010-06-27. 
  4. ^ a b (Inggris) "The Role of Tau in Alzheimer's Disease and Related Disorders". Department of Neurobiology and Behavior and Institute for Memory Impairments and Neurological Disorders, University of California; Medeiros R, Baglietto-Vargas D, Laferla FM. Diarsipkan dari versi asli tanggal 2019-12-25. Diakses tanggal 2010-06-21. 
  5. ^ (Inggris) "Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention". Department of Neurochemistry New York State Institute for Basic Research in Developmental Disabilities; Iqbal K, Grundke-Iqbal I. Diarsipkan dari versi asli tanggal 2016-06-11. Diakses tanggal 2010-06-21. 
  6. ^ (Inggris) "Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration". Pathophysiology Department, Tongji Medical College, Huazhong University of Science & Technology; Wang JZ, Grundke-Iqbal I, Iqbal K. Diarsipkan dari versi asli tanggal 2017-07-15. Diakses tanggal 2010-06-21. 
  7. ^ (Inggris) "Inhibition of neurofibrillary degeneration: a promising approach to Alzheimer's disease and other tauopathies". Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities; Iqbal K, Grundke-Iqbal I. Diarsipkan dari versi asli tanggal 2023-07-21. Diakses tanggal 2010-06-21. 
  8. ^ (Inggris) "Mechanism of neurofibrillary degeneration and pharmacologic therapeutic approach". New York State Institute for Basic Research in Developmental Disabilities; Iqbal K, Alonso AD, Gondal JA, Gong CX, Haque N, Khatoon S, Sengupta A, Wang JZ, Grundke-Iqbal I. Diarsipkan dari versi asli tanggal 2019-04-10. Diakses tanggal 2010-06-21. 
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