Neuroendocrine Aspects of the Molecular Chaperones ADNF and ADNP

Gozes, Illana; Vulih, Inna; Spivak-Pohis, Irit; Furman, Sharon

doi:10.1017/cbo9780511546310.016

Cited by 5 publications

(6 citation statements)

References 45 publications

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“…These results suggested a direct association between hsp60 and ADNF-like proteins [5]. Our previous manuscript [5] further included a review on mechanistic studies on ADNF-9, indicating protection against oxidative stress through maintenance of mitochondrial function and a reduction in the accumulation of intracellular reactive oxygen species [8], [11]. In the target neurons, ADNF-9 regulates transcriptional activation associated with neuroprotection (nuclear factorkappaB [11]), promotes axonal elongation through transcriptionally regulated cAMP-dependent mechanisms [12] and increases chaperonin expression (heat shock protein 60), thus providing cellular protection against the -amyloid peptide [13].…”

Section: Introductionmentioning

confidence: 76%

“…Other studies, with transfected glioblastoma cells including an hsp60 expression vector, indicated that increases in hsp60 resulted in increases in ADNF-like immunoreactivity in the intracellular and the extracellular milieu. These results suggested a direct association between hsp60 and ADNF-like proteins [5]. Our previous manuscript [5] further included a review on mechanistic studies on ADNF-9, indicating protection against oxidative stress through maintenance of mitochondrial function and a reduction in the accumulation of intracellular reactive oxygen species [8], [11].…”

Section: Introductionmentioning

confidence: 96%

“…Its primary structure contains sequences which are similar to sequences in heat shock protein 60 (hsp60) [4,5]. ADNF demonstrated protection of neuronal populations against multiple toxicities [3].…”

Section: Introductionmentioning

confidence: 99%

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Protection Against Tauopathy by the Drug Candidates NAP (Davunetide) and D-SAL: Biochemical, Cellular and Behavioral Aspects

Shiryaev¹,

Pikman²,

Giladi³

et al. 2011

CPD

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Activity-dependent neuroprotective protein (ADNP) is essential for brain formation and partial deficiency in ADNP results in cognitive deficits coupled with tauopathy and neuronal cell death. Our previous results indicated that a peptide snippet from ADNP, NAPVSIPQ (NAP, generic name, davunetide) can restore in part ADNP deficiencies. NAP interacts with tubulin and this interaction is displaced by the NAP related peptide that is derived from activity-dependent neurotrophic factor (ADNF), SALLRSIPA (SAL) and its all D-amino acid peptide derivative (D-SAL, also known as AL-309). Both NAP and D-SAL were shown to protect neurons against amyloid beta toxicity however the mechanism of protection is still under investigation. In addition, NAP protects against tau hyperphosphorylation associated with ADNP deficiency, in vivo. To investigate whether the mechanism of in vitro neuroprotection relates to the in vivo protection against tauopathy and to draw potential additional parallelism between NAP and D-SAL, we asked if: 1]NAP and D-SAL protect against amyloid beta related tau hyperphosphorylation in vitro; and 2] D-SAL protects against haploinsufficiency in ADNP, inhibiting tauopathy in vivo. Assessment of NAP and D-SAL neuroprotection in primary cortical neuro-glial cultures treated with amyloid beta showed that both peptides reduced toxin-related neuronal damage and protected against tau hyperphosphorylation. In vivo, chronic D-SAL administration protected against tau hyperphosphorylation associated with ADNP deficiency (ADNP+/- mice), showing for the first time protection against deficits in odor discrimination and in social recognition. These studies associate neuroprotection in vivo and in vitro and provide a broad base for future drug development based on NAP and D-SAL against multiple neurodegenerative conditions.

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Section: Introductionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 96%

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Protection Against Tauopathy by the Drug Candidates NAP (Davunetide) and D-SAL: Biochemical, Cellular and Behavioral Aspects

Shiryaev¹,

Pikman²,

Giladi³

et al. 2011

CPD

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“…ADNP synthesis and secretion is induced by the neuroprotective vasoactive intestinal peptide [ 1 , 7 ]. Activity-dependent neuroprotective factor (ADNF) was isolated from conditioned medium of astrocytes treated with vasoactive intestinal peptide that, in turn, was initially found to be associated with embryonic development and brain protection [ 8 - 11 ]. The active core of ADNF, namely ADNF-9 (SALLRSIPA), exhibits structural and functional similarities with NAP [ 1 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

NAP and D-SAL: neuroprotection against the β amyloid peptide (1–42)

2008

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Introduction: NAP (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln, single amino acid letter code, NAPVSIPQ), an eight amino acid neuroprotective peptide derived from activity-dependent neuroprotective protein (ADNP), exhibits some structural similarity to activity-dependent neurotropic factor-9 (ADNF-9; Ser-Alal-Leu-Leu-Arg-Ser-Ile-Pro-Ala, SALLRSIPA). Both peptides are also active in the all D-amino acid conformation, termed D-NAP and D-SAL. Original results utilizing affinity chromatography coupled to mass spectrometry identified tubulin, the subunit protein of microtubules, as the major NAP-associating protein in brain. The NAP-tubulin association was found to be diminished in the presence of ADNF-9, D-NAP, and D-SAL, suggesting a common target of neuroprotection. The β amyloid peptide interacts with microtubules, and previous studies have demonstrated protection against β amyloid (25-35) toxicity by NAP and ADNF-9. NAP also inhibits β amyloid (25-35 and 1-40) aggregation.

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“…Whereas external application of short insoluble peptide aggregates, such as β-amyloid, can induce neural cell death in vitro, soluble neurotrophic peptides, such as the vasoactive intestinal peptide (VIP) and the activity-dependent neurotrophic factor (ADNF), can protect neural cells from β-amyloid induced apoptosis (for a review, see Gozes et al, 2005). Hence, VIP-stimulated astrocytes can secrete short peptides, such as ADNF, which, already at femtomolar concentrations, can increase the levels of mitochondrial Hsp60 while protecting neurons from death associated with a broad range of toxins, including those related to Alzheimer's disease (Zamostiano et al, 1999).…”

Section: Hsp-inducing Peptidesmentioning

confidence: 99%

Chaperones and Proteases: Cellular Fold-Controlling Factors of Proteins in Neurodegenerative Diseases and Aging

Hinault

Ben‐Zvi

Goloubinoff

2006

JMN

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The formation of toxic protein aggregates is a common denominator to many neurodegenerative diseases and aging. Accumulation of toxic, possibly infectious protein aggregates induces a cascade of events, such as excessive inflammation, the production of reactive oxygen species, apoptosis and neuronal loss. A network of highly conserved molecular chaperones and of chaperone-related proteases controls the fold-quality of proteins in the cell. Most molecular chaperones can passively prevent protein aggregation by binding misfolding intermediates. Some molecular chaperones and chaperone-related proteases, such as the proteasome, can also hydrolyse ATP to forcefully convert stable harmful protein aggregates into harmless natively refoldable, or protease-degradable, polypeptides. Molecular chaperones and chaperone-related proteases thus control the delicate balance between natively folded functional proteins and aggregation-prone misfolded proteins, which may form during the lifetime and lead to cell death. Abundant data now point at the molecular chaperones and the proteases as major clearance mechanisms to remove toxic protein aggregates from cells, delaying the onset and the outcome of protein-misfolding diseases. Therapeutic approaches include treatments and drugs that can specifically induce and sustain a strong chaperone and protease activity in cells and tissues prone to toxic protein aggregations.

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Neuroendocrine Aspects of the Molecular Chaperones ADNF and ADNP

Cited by 5 publications

References 45 publications

Protection Against Tauopathy by the Drug Candidates NAP (Davunetide) and D-SAL: Biochemical, Cellular and Behavioral Aspects

Protection Against Tauopathy by the Drug Candidates NAP (Davunetide) and D-SAL: Biochemical, Cellular and Behavioral Aspects

NAP and D-SAL: neuroprotection against the β amyloid peptide (1–42)

Chaperones and Proteases: Cellular Fold-Controlling Factors of Proteins in Neurodegenerative Diseases and Aging

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