Amyloid beta soluble forms and plasminogen activation system in Alzheimer's disease: Consequences on extracellular maturation of brain-derived neurotrophic factor and therapeutic implications

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F19%3A10394274" target="_blank" >RIV/00064203:_____/19:10394274 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/19:10394274 RIV/00159816:_____/19:00071037

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=41zjwqLyQz" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=41zjwqLyQz</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/cns.13082" target="_blank" >10.1111/cns.13082</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Amyloid beta soluble forms and plasminogen activation system in Alzheimer's disease: Consequences on extracellular maturation of brain-derived neurotrophic factor and therapeutic implications

Popis výsledku v původním jazyce

Soluble oligomeric forms of amyloid beta (A beta) play an important role in causing the cognitive deficits in Alzheimer&apos;s disease (AD) by targeting and disrupting synaptic pathways. Thus, the present research is directed toward identifying the neuronal pathways targeted by soluble forms and, accordingly, develops alternative therapeutic strategies. The neurotrophin brain-derived neurotrophic factor (BDNF) is synthesized as a precursor (pro-BDNF) which is cleaved extracellularly by plasmin to release the mature form. The conversion from pro-BDNF to BDNF is an important process that regulates neuronal activity and memory processes. Plasmin-dependent maturation of BDNF in the brain is regulated by plasminogen activator inhibitor-1 (PAI-1), the natural inhibitor of tissue-type plasminogen activator (tPA). Therefore, tPA/PAI-1 system represents an important regulator of extracellular BDNF/pro-BDNF ratio. In this review, we summarize the data on the components of the plasminogen activation system and on BDNF in AD. Moreover, we will hypothesize a possible pathogenic mechanism caused by soluble A beta forms based on the effects on tPA/PAI-1 system and on the consequence of an altered conversion from pro-BDNF to the mature BDNF in the brain of AD patients. Translation into clinic may include a better characterization of the disease stage and future direction on therapeutic targets.

Název v anglickém jazyce

Amyloid beta soluble forms and plasminogen activation system in Alzheimer's disease: Consequences on extracellular maturation of brain-derived neurotrophic factor and therapeutic implications

Popis výsledku anglicky

Soluble oligomeric forms of amyloid beta (A beta) play an important role in causing the cognitive deficits in Alzheimer&apos;s disease (AD) by targeting and disrupting synaptic pathways. Thus, the present research is directed toward identifying the neuronal pathways targeted by soluble forms and, accordingly, develops alternative therapeutic strategies. The neurotrophin brain-derived neurotrophic factor (BDNF) is synthesized as a precursor (pro-BDNF) which is cleaved extracellularly by plasmin to release the mature form. The conversion from pro-BDNF to BDNF is an important process that regulates neuronal activity and memory processes. Plasmin-dependent maturation of BDNF in the brain is regulated by plasminogen activator inhibitor-1 (PAI-1), the natural inhibitor of tissue-type plasminogen activator (tPA). Therefore, tPA/PAI-1 system represents an important regulator of extracellular BDNF/pro-BDNF ratio. In this review, we summarize the data on the components of the plasminogen activation system and on BDNF in AD. Moreover, we will hypothesize a possible pathogenic mechanism caused by soluble A beta forms based on the effects on tPA/PAI-1 system and on the consequence of an altered conversion from pro-BDNF to the mature BDNF in the brain of AD patients. Translation into clinic may include a better characterization of the disease stage and future direction on therapeutic targets.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

CNS Neuroscience and Therapeutics

ISSN

1755-5930

e-ISSN

—

Svazek periodika

25

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

CN - Čínská lidová republika

Počet stran výsledku

11

Strana od-do

303-313

Kód UT WoS článku

000459319200001

EID výsledku v databázi Scopus

2-s2.0-85056143149