Scientists know that faulty proteins can cause harmful deposits or "aggregates" in neurological disorders such as Alzheimer's and Parkinson's disease. Although the causes of these protein deposits remain a mystery, it is known that abnormal aggregates can result when cells fail to
transmit proper genetic information to proteins.
Researchers from the University of California San Diego first highlighted this cause of brain disease more than 10 years ago. Today, they have identified a gene, Ankrd16, that prevents the protein aggregates they originally observed. Usually, the information transfer from gene to protein is carefully controlled — biologically "proofread" and corrected — to avoid the production of improper proteins.
Recent research identified that Ankrd16 rescued specific neurons — called Purkinje cells — that die when proofreading fails. Without normal levels of Ankrd16, these nerve cells, located in the cerebellum, incorrectly activate the amino acid serine, which is then improperly incorporated into proteins, causing protein aggregation.
The levels of Ankrd16 are normally low in Purkinje cells, making these neurons vulnerable to proofreading defects. Raising the level of Ankrd16 protects these cells from dying, while removing Ankrd16 from other neurons in mice with a proofreading deficiency caused widespread buildup of abnormal proteins and ultimately neuronal death. The researchers note that only a few modifier genes of disease mutations such as Ankrd16 have been identified and a modifier-based mechanism for understanding the underlying pathology of neurodegenerative diseases may be a promising route to understanding disease development.
Reprinted by materials provided by: The University of California – San Diego
Wanasayansi wanajua kwamba protini zenye kasoro zinaweza kusababisha madini yenye madhara au "mkusanyiko" katika magonjwa ya neva kama vile ugonjwa wa Alzheimer na Parkinson. Ingawa sababu za kuhifadhiwa kwa protini hizo bado ni fumbo, inajulikana kwamba kuunganishwa kwa protini zisizo za kawaida kunaweza kutokea wakati chembe zinashindwa kupitisha habari sahihi ya urithi kwa protini. Watafiti kutoka Chuo Kikuu cha California huko San Diego walichunguza kwa mara ya kwanza sababu hii ya ugonjwa wa ubongo zaidi ya miaka kumi iliyopita. Kwa mfano, kuna chembe ya urithi inayoitwa Ankyrid-16 ambayo inazuia protini zinazozunguka kwenye mwili. Kwa kawaida, uhamisho wa habari kutoka kwa jeni hadi protini unadhibitiwa kwa uangalifu - "kusahihishwa" na kurekebishwa kibiolojia - ili kuepuka utengenezaji wa protini zisizofaa. Utafiti wa hivi karibuni uligundua kwamba Ankrd16 iliokoa neuroni maalum - zinazoitwa seli za Purkinje - ambazo hufa wakati usomaji wa usahihi unashindwa. Bila viwango vya kawaida vya Ankyrie D16, seli hizi za neva, ziko katika cerebellum, huamsha kwa makosa asidi ya amino serine, ambayo kisha huingizwa vibaya katika protini, na kusababisha mkusanyiko wa protini. Kiwango cha Ankyrie D16 ni chini katika seli za Purkinje, na hivyo kufanya seli hizi za neva kuwa hatari kwa kasoro za usomaji. Kuongeza kiwango cha Ankyrie D16 husaidia kuzuia seli hizo kufa, wakati kuondoa Ankyrie D16 kutoka kwa neuroni nyingine katika panya na upungufu wa usomaji wa usahihi husababisha mkusanyiko mkubwa wa protini zisizo za kawaida na hatimaye kifo cha neuroni. Watafiti wanasema kuwa ni jeni chache tu za mabadiliko ya ugonjwa kama Ankyrie16 ambazo zimetambuliwa na utaratibu wa msingi wa mabadiliko ya kuelewa ugonjwa wa msingi wa magonjwa ya neurodegenerative inaweza kuwa njia ya kuahidi kuelewa maendeleo ya ugonjwa. Reprinted na vifaa zinazotolewa na: Chuo Kikuu cha California <unk> San Diego