Pharmacological Actions of Recombinant Human Nerve Growth Factor on Lesioned Central Cholinergic Neurons: Rationale for the Treatment of Alzheimer’s Disease

1991 ◽  
pp. 397-403
Author(s):  
Paul A. Lapchak ◽  
Franz Hefti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cholinergic Neurons ◽  
Nerve Growth ◽  
Human Nerve

scholarly journals The Nerve Growth Factor Metabolic Pathway Dysregulation as Cause of Alzheimer’s Cholinergic Atrophy

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 16
Author(s):  
Sonia Do Carmo ◽  
Benjamin Kannel ◽  
A. Claudio Cuello
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Metabolic Pathway ◽  
Cholinergic Neurons ◽  
Neuronal System ◽  
Cognitive Mechanisms ◽  
Nerve Growth ◽  
Cholinergic Phenotype

The cause of the loss of basal forebrain cholinergic neurons (BFCNs) and their terminal synapses in the cerebral cortex and hippocampus in Alzheimer’s disease (AD) has provoked a decades-long controversy. The cholinergic phenotype of this neuronal system, involved in numerous cognitive mechanisms, is tightly dependent on the target-derived nerve growth factor (NGF). Consequently, the loss of BFCNs cholinergic phenotype in AD was initially suspected to be due to an NGF trophic failure. However, in AD there is a normal NGF synthesis and abundance of the NGF precursor (proNGF), therefore the NGF trophic failure hypothesis for the atrophy of BCNs was abandoned. In this review, we discuss the history of NGF-dependency of BFCNs and the atrophy of these neurons in Alzheimer’s disease (AD). Further to it, we propose that trophic factor failure explains the BFCNs atrophy in AD. We discuss evidence of the occurrence of a brain NGF metabolic pathway, the dysregulation of which, in AD explains the severe deficiency of NGF trophic support for the maintenance of BFCNs cholinergic phenotype. Finally, we revise recent evidence that the NGF metabolic dysregulation in AD pathology starts at preclinical stages. We also propose that the alteration of NGF metabolism-related markers in body fluids might assist in the AD preclinical diagnosis.

scholarly journals The Role of Astrocytes in the Cause of Alzheimer's Disease

2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Nadia Priyam ◽  
Andrew Savoy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cholinergic Neurons ◽  
Amyloid Plaques ◽  
Nerve Growth ◽  
App Processing ◽  
Cholinergic Signaling

There are three leading hypotheses about the cause of Alzheimer’s Disease (AD): the cholinergic theory, where there is a loss of cholinergic neurons; the amyloid hypothesis, where there is an abnormal buildup of amyloid plaques; and the neurotrophic unbalance hypothesis, which states that AD-related loss of cholinergic signaling and altered amyloid precursor protein (APP) processing are due to alterations in nerve growth factor (NGF). This would ultimately mean that the loss of cholinergic neurons and a buildup of amyloid plaques are due to NGF alterations. Astrocytes are involved in the production of amyloid-beta, inflammation responses, and nerve growth. Therefore, astrocytes are an essential component of all three AD hypotheses. This paper will discuss various known and hypothesized ways that astrocytes affect the symptoms and possible causes of AD.

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