Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis.
Alzheimers Dement
; 18(11): 2327-2340, 2022 11.
Article
de En
| MEDLINE
| ID: mdl-35234334
ABSTRACT
OBJECTIVE:
Evaluating the efficacy of 3,6'-dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline.BACKGROUND:
Amyloid-ß (Aß) or tau-focused clinical trials have proved unsuccessful in mitigating AD-associated cognitive impairment. Identification of new drug targets is needed. Neuroinflammation is a therapeutic target in neurodegenerative disorders, and TNF-α a pivotal neuroinflammatory driver. NEWHYPOTHESIS:
AD-associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aß generation will define the role of neuroinflammation in AD progression. MAJOR CHALLENGES Difficulty of TNF-α-lowering compounds reaching brain, and identification of a therapeutic-time window to preserve the beneficial role of neuroinflammatory processes. LINKAGE TO OTHER MAJOR THEORIES Microglia/astroglia are heavily implicated in maintenance of synaptic plasticity/function in healthy brain and are disrupted by Aß. Mitigation of chronic gliosis can restore synaptic homeostasis/cognitive function.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maladie d'Alzheimer
/
Dysfonctionnement cognitif
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Alzheimers Dement
Année:
2022
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique