TY - JOUR
T1 - Apoptotic neurons and amyloid-beta clearance by phagocytosis in Alzheimer's disease
T2 - Pathological mechanisms and therapeutic outlooks
AU - Tajbakhsh, Amir
AU - Read, Morgayn
AU - Barreto, George E.
AU - Ávila-Rodriguez, Marco
AU - Gheibi-Hayat, Seyed Mohammad
AU - Sahebkar, Amirhossein
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/3/15
Y1 - 2021/3/15
N2 - Neuronal survival and axonal renewal following central nervous system damage and in neurodegenerative illnesses, such as Alzheimer's disease (AD), can be enhanced by fast clearance of neuronal apoptotic debris, as well as the removal of amyloid beta (Aβ) by phagocytic cells through the process of efferocytosis. This process quickly inhibits the release of proinflammatory and antigenic autoimmune constituents, enhancing the formation of a microenvironment vital for neuronal survival and axonal regeneration. Therefore, the detrimental features associated with microglial phagocytosis uncoupling, such as the accumulation of apoptotic cells, inflammation and phagoptosis, could exacerbate the pathology in brain disease. Some mechanisms of efferocytosis could be targeted by several promising agents, such as curcumin, URMC-099 and Y–P30, which have emerged as potential treatments for AD. This review aims to investigate and update the current research regarding the signaling molecules and pathways involved in efferocytosis and how these could be targeted as a potential therapy in AD.
AB - Neuronal survival and axonal renewal following central nervous system damage and in neurodegenerative illnesses, such as Alzheimer's disease (AD), can be enhanced by fast clearance of neuronal apoptotic debris, as well as the removal of amyloid beta (Aβ) by phagocytic cells through the process of efferocytosis. This process quickly inhibits the release of proinflammatory and antigenic autoimmune constituents, enhancing the formation of a microenvironment vital for neuronal survival and axonal regeneration. Therefore, the detrimental features associated with microglial phagocytosis uncoupling, such as the accumulation of apoptotic cells, inflammation and phagoptosis, could exacerbate the pathology in brain disease. Some mechanisms of efferocytosis could be targeted by several promising agents, such as curcumin, URMC-099 and Y–P30, which have emerged as potential treatments for AD. This review aims to investigate and update the current research regarding the signaling molecules and pathways involved in efferocytosis and how these could be targeted as a potential therapy in AD.
KW - Alzheimer's disease
KW - Amyloid beta
KW - Apoptosis
KW - Corpse clearance
KW - Efferocytosis
KW - Microglia
KW - Phagocytic clearance
KW - “Eat-me” signal
UR - http://www.scopus.com/inward/record.url?scp=85099633464&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2021.173873
DO - 10.1016/j.ejphar.2021.173873
M3 - Review article
C2 - 33460611
AN - SCOPUS:85099633464
SN - 0014-2999
VL - 895
SP - -
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
M1 - 173873
ER -