As the population ages,the burden of age-related diseases becomes greater.Currently,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common form.However,it is becoming cle...As the population ages,the burden of age-related diseases becomes greater.Currently,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common form.However,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of cSVD.The term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CSVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).展开更多
Leucine rich repeat proteins have gained considerable interest as therapeutic targets due to their expression and biological activity within the central nervous system. LINGO-1 has received particular attention since ...Leucine rich repeat proteins have gained considerable interest as therapeutic targets due to their expression and biological activity within the central nervous system. LINGO-1 has received particular attention since it inhibits axonal regeneration after spinal cord injury in a Rho A dependent manner while inhibiting leucine rich repeat and immunoglobulin-like domain-containing protein 1（LINGO-1） disinhibits neuron outgrowth. Furthermore, LINGO-1 suppresses oligodendrocyte precursor cell maturation and myelin production. Inhibiting the action of LINGO-1 encourages remyelination both in vitro and in vivo. Accordingly, LINGO-1 antagonists show promise as therapies for demyelinating diseases. An analogous protein to LINGO-1, amphoterin-induced gene and open reading frame-3（AMIGO3）, exerts the same inhibitory effect on the axonal outgrowth of central nervous system neurons, as well as interacting with the same receptors as LINGO-1. However, AMIGO3 is upregulated more rapidly after spinal cord injury than LINGO-1. We speculate that AMIGO3 has a similar inhibitory effect on oligodendrocyte precursor cell maturation and myelin production as with axogenesis. Therefore, inhibiting AMIGO3 will likely encourage central nervous system axonal regeneration as well as the production of myelin from local oligodendrocyte precursor cell, thus providing a promising therapeutic target and an area for future investigation.展开更多
文摘As the population ages,the burden of age-related diseases becomes greater.Currently,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common form.However,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of cSVD.The term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CSVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).
基金supported by a grant from The University of Birmingham
文摘Leucine rich repeat proteins have gained considerable interest as therapeutic targets due to their expression and biological activity within the central nervous system. LINGO-1 has received particular attention since it inhibits axonal regeneration after spinal cord injury in a Rho A dependent manner while inhibiting leucine rich repeat and immunoglobulin-like domain-containing protein 1（LINGO-1） disinhibits neuron outgrowth. Furthermore, LINGO-1 suppresses oligodendrocyte precursor cell maturation and myelin production. Inhibiting the action of LINGO-1 encourages remyelination both in vitro and in vivo. Accordingly, LINGO-1 antagonists show promise as therapies for demyelinating diseases. An analogous protein to LINGO-1, amphoterin-induced gene and open reading frame-3（AMIGO3）, exerts the same inhibitory effect on the axonal outgrowth of central nervous system neurons, as well as interacting with the same receptors as LINGO-1. However, AMIGO3 is upregulated more rapidly after spinal cord injury than LINGO-1. We speculate that AMIGO3 has a similar inhibitory effect on oligodendrocyte precursor cell maturation and myelin production as with axogenesis. Therefore, inhibiting AMIGO3 will likely encourage central nervous system axonal regeneration as well as the production of myelin from local oligodendrocyte precursor cell, thus providing a promising therapeutic target and an area for future investigation.
